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Aim: The immune status of children recovering from SARS‐CoV‐2 infection is not completely understood. We describe IgG antispike persistence in children infected during the first two pandemic waves. In addition, we compared with healthy controls their leukocyte populations and CD64 expression. Methods: Cross‐sectional study. Carried out from October 2021 to February 2022 in nonreinfected and nonvaccinated children with SARS‐CoV‐2 in 2020. The presence of antispike IgG was studied using chemiluminescent immunoassay. Leukocyte populations were analysed using flow cytometry and marked for CD45, CD4, CD8 and CD64. Statistical minor than 0.05 was considered significant. Results: One hundred and eighty‐three control and 77 patients were included. IgG antispike determinations were performed after a median of 501 days (262–464); 52 of 77 children were positive. Cases showed significantly higher percentages of monocytes, lymphocytes, CD8+ and CD4+. In addition, CD64 expression was higher in monocytes and neutrophils. The presence of IgG antispike was accompanied by a higher percentage of CD64+ neutrophils. Conclusion: In our series, the SARS‐CoV‐2 IgG antispike protein was usually positive beyond 1 year after infection. Furthermore, leukocyte populations from cases differ from controls, with higher CD64 expression on neutrophils and monocytes. Prospective clinical observations are required to confirm the implications of these findings. [ABSTRACT FROM AUTHOR]

Within‐host parasite interactions can be mediated by the host and changes in host phenotypes often serve as indicators of the presence or intensity of parasite interactions.Parasites like helminths induce a range of physiological, morphological and immunological changes in hosts that can drive bottom‐up (resource‐mediated) or top‐down (immune‐mediated) interactions with co‐infecting parasites. Although top‐down and bottom‐up interactions are typically studied in isolation, the diverse phenotypic changes induced by parasite infection may serve as a useful tool for understanding if, and when, these processes act in concert.Using an anthelmintic treatment study of African buffalo, Syncerus caffer, we tracked changes in host immunological and morphological phenotypes during helminth‐coccidia co‐infection to investigate their role in driving independent and combinatorial bottom‐up and top‐down parasite interactions. We also examined repercussions for host fitness.Clearance of a blood‐sucking helminth, Haemonchus, from the host gastrointestinal tract induced a systemic Th2 immune phenotype, while clearance of a tissue‐feeding helminth, Cooperia, induced a systemic Th1 phenotype. Furthermore, the Haemonchus‐associated systemic Th2 immune phenotype drove simultaneous top‐down and bottom‐up effects that increased coccidia shedding by changing the immunological and morphological landscapes of the intestine.Higher coccidia shedding was associated with lower host body condition, a lower chance of pregnancy and older age at first pregnancy, suggesting that coccidia infection imposed significant condition and reproductive costs on the host.Our findings suggest that top‐down and bottom‐up interactions may commonly co‐occur and that tracking key host phenotypes that change in response to infection can help uncover complex pathways by which parasites interact. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a progressive severe muscle‐wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germ‐free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD. Synopsis: The susceptibility of DMD patients to inflammatory events cannot solely be explained by skeletal muscle genetic defects but rather favors a new paradigm linking development of chronic inflammation with a strict regulation between epigenetics factors and degenerative environment. Gut microbiota–specific alterations (dysbiosis) correlate with the dystrophic pathology in mdx mice, influencing muscle immunity and fibrosis.Dysbiotic mdx microbiota induces a decreased innate immune response and altered muscle metabolism.The study of the dysregulated immune system‐microbiota axis in mdx mice highlights the importance of microbiota as a potential target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model. Intradermal injection of low-dose α-melittin-NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and α-melittin-NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low-dose α-melittin-NPs leads to relief of antigen recognition-induced effector T cell arrest in the dermis and inhibited allergen-specific T cell proliferation and activation. Significantly, this approach successfully controls Th1-type cytokine release in the ACD model and restricts Th2-type cytokine and IgE release in the AD-like model. Overall, intradermal delivery of low-dose α-melittin-NPs efficiently elicits immunosuppression against T cell-mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region. [ABSTRACT FROM AUTHOR]

The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway is an essential component of the innate immune system and is central to the identification of abnormal DNA leakage caused by ionising radiation (IR) damage. Cell‐intrinsic cGAS–STING initiation has been revealed to have tremendous potential for facilitating interferon synthesis and T‐cell priming. Targeting the cGAS–STING axis has been proposed as a strategy to improve radiosensitivity or enhance immunosurveillance. However, due to the complex biology of the irradiated tumour microenvironment and the extensive involvement of the cGAS–STING pathway in various physiological and pathological processes, many defects in this strategy limit the therapeutic effect. Here, we outline the molecular mechanisms by which IR activates the cGAS–STING pathway and analyse the dichotomous roles of the cGAS–STING pathway in modulating cancer immunity after radiotherapy (RT). Then, based on the crosstalk between the cGAS–STING pathway and other signalling events induced by IR, such as necroptosis, autophagy and other cellular effects, we discuss the immunomodulatory actions of the broad cGAS–STING signalling network in RT and their potential therapeutic applications. Finally, recent advances in combination therapeutic strategies targeting cGAS–STING in RT are explored. [ABSTRACT FROM AUTHOR]

Background: Numerous patient‐based studies have highlighted the protective role of immunoglobulin E‐mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection. Methods: An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1‐KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA‐sequencing. Peripheral as well as tumor‐associated immune cells were characterized by flow cytometry. The impact of allergy‐related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets. Results: We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro‐inflammatory‐like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T‐cells in the circulation as well as tumor‐infiltrating CD4+T‐cells. The survival benefit conferred by AAI was lost in mice devoid of adaptive immunity. Conclusion: Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy‐induced immune protection against GBM. [ABSTRACT FROM AUTHOR]

A total of 300 laying Japanese quails (230.10 ± 20 g body weight) divided into four groups (15 birds in 5 replicates/group) were used to examine the impacts of dietary sodium humate (SH) supplementation at levels of 0% (control diet), 0.2%, 0.4% and 0.6% on egg variables and physiological merits of laying quails for 10 weeks under heat stress conditions (15 June and 23 August 2021). Results showed 0.4% SH increased (p < 0.05) weight (12.27 vs. 11.91 g), production (79.84% vs. 69.20%), mass (597.13 vs. 510.48 g) and brokenness (2.8% vs. 5.4%) of eggs as compared to control. Egg shape, shell thickness, shell strength and cholesterol content as well as feed conversion ratio were higher (80.2, 295.8 µm, 1.468 kg/cm,2 11.08 mg/g and 2.69, p < 0.05) in 0.4% SH than in control group (75.2, 279.0 µm, 1.304 kg/cm,2 14.94 mg/g and 2.76). Feed intake, percentages of eggs' shells, yolk, albumen and serum biochemistry (total protein, albumin, AST and HDL) were not altered with the dietary SH. Birds fed on SH diets showed higher levels of globulin, calcium and phosphorus, as well as lower contents of albumin/globulin ratio, triglycerides, cholesterol, corticosterone compared with the control. Regression analysis of antioxidants expected higher total antioxidant capacity (TAC), superoxide dismutase, glutathione peroxidase at 0.35%, and glutathione at 0.40% SH, while the lowest concentration of malondialdehyde was computed at 0.45%. Similarly, immunoglobulins (IgG and IgM) maximum values were determined at 0.35% and 0.40% levels. Moreover, the concentration of tumour necrosis factor‐alpha increased (p < 0.05) in all SH levels as compared to the control group. It is conceivable to conclude that the dietary implementation of SH at a level of 0.4% improved egg variables and well‐being aspects of laying quail exposed to heat stress conditions. [ABSTRACT FROM AUTHOR]

Summary: Expression of OXIDATIVE SIGNAL‐INDUCIBLE1 (OXI1) is induced by a number of stress conditions and regulates the interaction of plants with pathogenic and beneficial microbes.In this work, we generated Arabidopsis OXI1 knockout and genomic OXI1 overexpression lines and show by transcriptome, proteome, and metabolome analysis that OXI1 triggers ALD1, SARD4, and FMO1 expressions to promote the biosynthesis of pipecolic acid (Pip) and N‐hydroxypipecolic acid (NHP).OXI1 contributes to enhanced immunity by induced SA biosynthesis via CBP60g‐induced expression of SID2 and camalexin accumulation via WRKY33‐targeted transcription of PAD3. OXI1 regulates genes involved in reactive oxygen species (ROS) generation such as RbohD and RbohF. OXI1 knock out plants show enhanced expression of nuclear and chloroplast genes of photosynthesis and enhanced growth under ambient conditions, while OXI1 overexpressing plants accumulate NHP, SA, camalexin, and ROS and show a gain‐of‐function (GOF) cell death phenotype and enhanced pathogen resistance. The OXI1 GOF phenotypes are completely suppressed when compromising N‐hydroxypipecolic acid (NHP) synthesis in the fmo1 or ald1 background, showing that OXI1 regulation of immunity is mediated via the NHP pathway.Overall, these results show that OXI1 plays a key role in basal and effector‐triggered plant immunity by regulating defense and programmed cell death via biosynthesis of salicylic acid, N‐hydroxypipecolic acid, and camalexin. [ABSTRACT FROM AUTHOR]

Zinc homeostatic medicine is of great potential for cancer chemo‐immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+‐mediated immune responses. In this work, we developed a novel cyclometalated PtIV‐terthiophene complex, Pt3, that not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level of zinc regulatory proteins, excess accumulation of Zn2+ in cytoplasm, and down‐regulation of metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption of zinc and redox homeostasis in response to Pt3 treatment activated gasdermin‐D mediated pyroptosis accompanied by cytoskeleton remodeling, thus releasing pro‐inflammatory cytokines to promote dendritic cell (DC) maturation and T cell tumor‐infiltration, eventually eliminating both primary and distant tumors in vivo. As far as we know, this is the first metal complex that can regulate zinc homeostasis to activate antitumor immunity. [ABSTRACT FROM AUTHOR]

Background and objective: Periodontitis (PD) is a dysbiotic disease of tooth-supporting structures that has been associated with various systemic diseases including rheumatoid arthritis (RA). To date, evidence demonstrated increased prevalence of RA among PD patients and postulated PD to have a role in the development of autoantibodies in RA patients. Therefore, a systematic review was conducted to assess the available evidence to ascertain the effect of PD on levels of autoantibodies in the serum, saliva and gingival crevicular fluid (GCF) of RA patients. Material and methods: The systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Relevant literature was searched from PubMed, Web of Science, Scopus and Ebscohost databases from inception until 31 August 2020. The risk of bias in each study was determined based on the Newcastle–Ottawa Scale tool. Results from random-effect meta-analyses were presented as summary estimates of odds ratios (ORs) for seropositivity and standardised mean difference (SMD) of autoantibody levels with 95% confidence intervals. Sensitivity tests and meta-regression were performed to assess the robustness of the results and potential cause of heterogeneity. Results: The electronic and manual searches gathered 932 articles. Following screening and full-text assessment, a total of 29 studies were included in the analysis. Twenty-eight published observational studies were included in the quantitative analysis in the form of random-effect meta-analysis which revealed that PD was associated with anti-citrullinated proteins autoantibodies (ACPAs) and Rheumatoid Factor (RF) seropositive RA patients (OR for ACPA seropositivity: 1.82; 95% CI: 1.13–2.93) (OR for RF seropositivity: 1.53; 95% CI: 1.05–2.24). Also, RA patients with PD had increased serum levels of ACPA and RF. However, high heterogeneity among studies' results, partially ascribed to the unstandardised case definition of PD and laboratory testing of autoantibodies. Apart from ACPA and RF in serum, studies which reported on other RA-related autoantibodies, as well as autoantibody levels in saliva and GCF were scarce. Conclusion: RA patients with PD tend to have greater ACPA and RF levels in their serum when compared with the RA patients without PD supporting the plausible role of PD in the development of systemic autoimmunity in RA patients. [ABSTRACT FROM AUTHOR]

To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID‐19‐BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti‐Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and nonresponsive patients was observed, considering a 5 log10 TTV copies/mL threshold to discriminate between the two groups. Moreover, for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/mL threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL), the most common leukemia in the western countries, is characterized by immunosuppression due to disease itself and cytotoxic treatments. Since the beginning of COVID‐19 pandemic, patients with CLL appear to be a vulnerable population. In addition, phase III mRNA vaccine trials did not provide information about the efficacy in immunocomprised population. In CLL, the antibody‐mediated response to SARS‐CoV‐2 vaccine is impaired. The goal of this study was to evaluate the effects of SARS‐CoV‐2 vaccination on humoral immune response and on cellular immunity in CLL patients. Humoral immune response to BNT162b2 messenger RNA COVID‐19 vaccine was evaluated in 44 CLL patients comprising 20 treatment‐naïve, 14 under treatment with ibrutinib and 10 in follow‐up after completion of therapy. A positive serological response to SARS‐CoV‐2 vaccination with IgG titers higher than 13 UA/ml was detected in 54.6% of CLL patients with a higher response in patients who obtained remission after treatment. Reduced antibody response was detected in patients under ibrutinib treatment. T‐cell response to overlapping pool of peptides representing the spike region was assessed in paired CLL samples collected before and after 1 month from the second dose of COVID‐19 vaccine in treatment‐naïve and ibrutinib‐treated CLL patients using cytokine secretion assay. Both CD3+ CD4+ and CD3+ CD8+ T cells are able to mount a cellular response to spike peptides with secretion of IFNγ and TNFα before and after vaccination in both treatment naïve and ibrutinib‐treated patients and this cellular immune response is independent by COVID‐19 vaccination. Collectively, T cell response to spike peptides appeared more blunted in CLL patients under treatment with ibrutinib compared to untreated ones. Our study supports the need for optimization of vaccination strategy to achieve an adequate immune response keeping strict preventive measures by CLL patients against COVID‐19. [ABSTRACT FROM AUTHOR]

The bidirectional interaction between the hypothalamic–pituitary‐gonadal (HPG) axis and the immune system plays a crucial role in the adaptation of an organism to its environment, its survival and the continuance of a species. Nonetheless, very little is known about this interaction among teleost, the largest group of extant vertebrates. Fishes being seasonal breeders, their immune system is exposed to seasonally changing levels of HPG hormones. On the contrary, the presence and infiltration of leukocytes, the expression of pattern recognition receptors as well as cytokines in gonads suggest their key role in teleostean gametogenesis as in the case of mammals. Moreover, the modulation of gametogenesis and steroidogenesis by lipopolysaccharide implicates the pathological significance of inflammation on reproduction. Thus, it is important to engage in the understanding of the interaction between these two important physiological systems, not only from a phylogenetic perspective but also due to the importance of fish as an important economic resource. In view of this, the authors have reviewed the crosstalk between the reproductive and immune systems in teleosts and tried to explore the importance of this interaction in their survival and reproductive fitness. [ABSTRACT FROM AUTHOR]

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID‐19. The efficacy of the COVID‐19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID‐19 vaccines have changed the clinical scenario of COVID‐19. Multisystem inflammatory syndrome in children (MIS‐C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long‐term symptoms of COVID‐19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID‐19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID‐19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID‐19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID‐19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID‐19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS‐CoV‐2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high‐risk groups, the development of MIS‐C and long COVID‐19. [ABSTRACT FROM AUTHOR]

Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity‐based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune‐mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro‐inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high‐risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti‐inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid‐mannan conjugates, which are next generation vaccines for allergen‐specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity‐based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

SUMMARY: Hydroxyurea (HU) (hydroxycarbamide) is used as a therapeutic option in β‐thalassaemia to increase fetal haemoglobin, which results in a reduced requirement for blood transfusion. However, a potential serious adverse effect of HU is neutropenia. Abnormal neutrophil maturation and function in β‐thalassaemia/HbE patients are well documented. This raises questions about the effect of the drug with regards to the immune response these patients. This study investigated the effects of HU treatment on both innate and adaptive immunity in a cross‐sectional study of 28 β‐thalassaemia/HbE patients who had received HU treatment (BE+HU) as compared with 22 β‐thalassaemia/HbE patients who had not received HU (BE‐HU) and 26 normal subjects. The expression of PU.1 and C/EBPβ, transcription factors, which are associated with neutrophil maturation, was significantly reduced in BE+HU patients as compared with BE‐HU patients and normal subjects. Interestingly, C3bR expression on neutrophils and their oxidative burst activity in BE+HU were restored to close to normal levels when compared with BE‐HU. There was no observed effect of HU on monocytes, myeloid derived suppressor cells (both granulocytic and monocytic subsets), CD4+T cells, CD8+T cells, complement levels and serum immunoglobulin levels in this study. The full immunophenotyping analysis in this study indicates that HU therapy in β‐thalassaemia/HbE patients does not significantly compromise the immune response. [ABSTRACT FROM AUTHOR]

SUMMARY: Sorghum is an important food and feed crop globally; its production is hampered by anthracnose disease caused by the fungal pathogen Colletotrichum sublineola (Cs). Here, we report identification and characterization of ANTHRACNOSE RESISTANCE GENE 2 (ARG2) encoding a nucleotide‐binding leucine‐rich repeat (NLR) protein that confers race‐specific resistance to Cs strains. ARG2 is one of a cluster of several NLR genes initially identified in the sorghum differential line SC328C that is resistant to some Cs strains. This cluster shows structural and copy number variations in different sorghum genotypes. Different sorghum lines carrying independent ARG2 alleles provided the genetic validation for the identity of the ARG2 gene. ARG2 expression is induced by Cs, and chitin induces ARG2 expression in resistant but not in susceptible lines. ARG2‐mediated resistance is accompanied by higher expression of defense and secondary metabolite genes at early stages of infection, and anthocyanin and zeatin metabolisms are upregulated in resistant plants. Interestingly, ARG2 localizes to the plasma membrane when transiently expressed in Nicotiana benthamiana. Importantly, ARG2 plants produced higher shoot dry matter than near‐isogenic lines carrying the susceptible allele suggesting an absence of an ARG2 associated growth trade‐off. Furthermore, ARG2‐mediated resistance is stable at a wide range of temperatures. Our observations open avenues for resistance breeding and for dissecting mechanisms of resistance. Significance Statement: Sorghum is a crop of global importance that is used for food, feed and biofuel. The crop feeds millions of people, especially small holder framers around the world. The productivity of sorghum is constrained by anthracnose diseases caused by the fungus Colletotrichum sublineola. Genetic resistance provides the most sustainable disease control method. We identified and characterized a sorghum anthracnose resistance gene encoding a nucleotide‐binding leucine‐rich repeat protein by exploring natural variation in the crop. Our findings will have significant implications for improvement of disease resistance in sorghum, as well as for future studies in the molecular genetics of pathogen resistance. [ABSTRACT FROM AUTHOR]

Background: There have been some reports that supplementation of fat could alleviate the negative effects of heat stress on performance in broilers. However, information regarding compensation for the adverse effects of heat stress with diets differing in fatty acids source on immune system, bone strength and carcass quality of heat‐distressed broilers is limited. Objectives: The objective of this study was to investigate the effects of diets differing in fat source on performance, immune system, bone strength, and carcass quality of heat‐distressed broilers. Methods: In a completely randomized design with 4 × 2 factorial arrangement of the treatments, 320 24‐day‐old Ross 308 chickens, with average initial weight of 1220 ± 10 g were divided into eight treatments included sesame oil, tallow, sunflower oil and palm oil in either 22 or 32 degree of centigrade temperature. The broiler performance of each fat source‐treated group was not different in this experiment and decreased significantly in heat stress condition. Results: Heat stress showed a significant increase on fat, energy and ash content of thigh muscle. Tibia absolute length, width, ash and bone breaking strength were affected by fat source and increased when sesame and sunflower oil were used. Data analysis revealed that hot temperature decreased tibia weight, length, width, ash and bone breaking strength. Heat stress led to decrease of immune system parameters. Conclusion: Results suggest that there is no beneficial effect of broiler performance due to adding different sources of fat in broiler chicken diet under hot condition. Furthermore, the unsaturated fatty acids could improve the profile of fatty acids in thigh and enhance immune responses in broiler chickens. [ABSTRACT FROM AUTHOR]

Vaccination against the SARS‐Cov‐2 virus is an effective way to protect against the disease and the severe course of COVID‐19. Forty‐nine fully vaccinated with mRNA vaccines (BNT162b2 or mRNA‐1273) SARS‐CoV‐2 infection‐naïve volunteers aged 33–89 were enrolled in the study. Evaluation of the cellular and humoral immune response was performed within 1 to 3 months (T1) and 6–9 months (T2) after the second injection, and within 2–3 months (T3) after a booster dose. Additionally, a comparative analysis of the specific immune status was made between two age groups—below 60 (n = 22) and over 60 (n = 27) years. SARS‐CoV‐2‐specific T‐cell response was evaluated by IFN‐γ‐producing spot forming cells (SFCs) using a standardized ELISPOT assay. Virus neutralizing antibodies (VNA) against SARS‐CoV‐2 were measured by a blocking ELISA test and spike protein specific IgG (S‐IgG) and IgA (S‐IgA) antibodies—by semiquantitative ELISA. IFN‐γ‐producing SFCs, S‐IgG, S‐IgA and VNA significantly decreased 6–9 months after the second dose. After the third injection S‐IgG and S‐IgA markedly increased compared to T2 and reached the levels at T1. Of note, the highest values of VNA were observed at T3. No differences in the tested immune parameters were found between the two age groups. Data obtained showed that for a long period—6–9 months after a full course of immunization with mRNA vaccine, immune reactivity is present, but both cellular and humoral immune responses gradually decrease. The administration of a third dose mainly restores the specific humoral immune response against the SARS‐CoV‐2 virus. [ABSTRACT FROM AUTHOR]

At least a dozen countries or states in the world have introduced vaccine injury compensation schemes. This paper argues that the Australian Government should introduce such a scheme, which may reduce litigation, and may improve consumer and provider confidence. The most important justification, however, is an ethical argument from justice and equity: introduction of a vaccine injury compensation scheme acknowledges the unique situation that routine childhood immunization is a public health measure, given and accepted in good faith, that may occasionally damage the recipient. [ABSTRACT FROM AUTHOR]

Hinze-Selch D. Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls. Bipolar Disord 2002: 4(Suppl. 1): 81–83. ©Blackwell Munksgaard, 2002 Bipolar disorder is the least studied among the three major psychiatric disorders of schizophrenia, major depression and bipolar disorder. Furthermore, investigations on infection and immunity in bipolar disorder make up only a small portion of the sparse research done on this disorder. However, there are reports that modulation of the immune system and certain infections might be associated with bipolar disorder and that there might be differences between bipolar and the other disorders. The purpose of this paper is to briefly review published data on these issues in bipolar versus the other disorders, and to present an ongoing clinical study on the putative involvement of infection with the parasite Toxoplasma gondii in these three major psychiatric disorders. [ABSTRACT FROM AUTHOR]

Insect pollinators provide crucial ecosystem services yet face increasing environmental pressures. The challenges posed by novel and reemerging pathogens on bee health means we need to improve our understanding of the immune system, an important barrier to infections and disease. Despite the importance of solitary bees, which are ecologically relevant, our understanding of the genomic basis and molecular mechanisms underlying their immune potential, and how intrinsic and extrinsic factors may influence it is limited. To improve our understanding of the genomic architecture underlying immunity of a key solitary bee pollinator, we characterized putative immune genes of the red mason bee, Osmia bicornis. In addition, we used publicly available RNA‐seq datasets to determine how sexes differ in immune gene expression and splicing but also how pesticide exposure may affect immune gene expression in females. Through comparative genomics, we reveal an evolutionarily conserved set of more than 500 putative immune‐related genes. We found genome‐wide patterns of sex‐biased gene expression, with greater enrichment of immune‐related processes among genes with higher constitutive expression in males than females. Our results also suggest an up‐regulation of immune‐related genes in response to exposure to two common neonicotinoids, thiacloprid and imidacloprid. Collectively, our study provides important insights into the gene repertoire, regulation and expression differences in the sexes of O. bicornis, as well as providing additional support for how neonicotinoids can affect immune gene expression, which may affect the capacity of solitary bees to respond to pathogenic threats. [ABSTRACT FROM AUTHOR]

New therapeutic modalities carry with them great promise for the treatment of rare diseases. They also present unique development challenges including immunogenicity, which can impact the safety and efficacy of those new modalities. In this review, an overview of the basic function of the immune system and its possible interaction with new therapeutic modalities is presented. A juxtaposition of immunogenicity in the rare disease space versus traditional clinical programs is hereby being proposed. A clinical pharmacology viewpoint of immunogenicity, proposed approaches to account for immunogenicity in clinical data, bioanalytical considerations, and effects of route of administration and production changes on immunogenicity are discussed. [ABSTRACT FROM AUTHOR]

It has been 25 years since we first described long‐lived memory plasma cells of the bone marrow, 13 years since we identified bone marrow resident memory T cells and 2 years since we showed that the bone marrow is also a preferred location of resident memory B cells. The bone marrow is increasingly recognized as a fundamental component of long‐lasting immunological memory, not only providing protective immunity but also fuelling chronic inflammation. We now understand that the bone marrow functions as the 'backbone' of immunological memory, hosting the memory plasma cells which provide not only humoral immunity but also memory B and T cells, which constitute 'reactive memory'. This knowledge now allows us to define true cellular 'correlates of protection' for systemic immunity, its quality and duration, as induced by infection and vaccination, something that has never been more important given the recent SARS‐CoV‐2 pandemic. While memory plasma cells of the bone marrow indicate long‐lasting humoral protection, memory T (and B) cells mobilized into the blood in secondary immune reactions indicate the strength of reactive memory. In this review, we have contextualized many of our own findings from the last two decades that have contributed to our understanding of how bone marrow‐resident memory cells provide local and systemic immunity. [ABSTRACT FROM AUTHOR]

Tumors are presently a major threat to human life and health. Malignant tumors are conventionally treated through radiotherapy and chemotherapy. However, traditional therapies yield unsatisfactory results due to high toxicity to the normal cells, inability to treat deep tumor tissues, and the possibility of inducing drug resistance in the tumor cells. This has caused immunotherapy to emerge as an effective and alternate treatment strategy. To overcome the limitations of the conventional treatments as well as to avert the risk of various drug resistance and cytotoxicity, bacterial anti‐tumor immunotherapy has raised the interest of researchers. This therapeutic strategy employs bacteria to specifically target and colonize the tumor tissues with preferential accumulation and proliferation. Such bacterial accumulation initiates a series of anti‐tumor immune responses, effectively eliminating the tumor cells. This immunotherapy can use the bacteria alone or concomitantly with the other methods. For example, the bacteria can deliver the anti‐cancer effect mediators by regulating the expression of the bacterial genes or by synthesizing the bioengineered bacterial complexes. This review will discuss the mechanism of utilizing bacteria in treating tumors, especially in terms of immune mechanisms. This could help in better integrating the bacterial method with other treatment options, thereby, providing a more effective, reliable, and unique treatment therapy for tumors. [ABSTRACT FROM AUTHOR]

The relative abundance of myeloid‐derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin‐specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)‐MDSCs, resulting in increased CD8+ T‐cell response and decelerated tumour growth. USP12‐knockout M‐MDSCs were less potent in inhibiting the proliferation of CD8+ T cells and their ability to secrete IFN‐γ. Furthermore, USP12 deficiency inhibited the suppressor function of M‐MDSCs by downregulating the negative regulatory molecules inducible nitric oxide synthase and PD‐L1, through deubiquitinating and stabilizing p65. Our results suggest that USP12 is a positive regulator of M‐MDSCs and may serve as a potential target for antitumor therapy. [ABSTRACT FROM AUTHOR]

Summary: The ongoing coronavirus disease 2019 (COVID‐19) pandemic has spurred rapid development of vaccines as part of the public health response. However, the general strategy used to construct recombinant trimeric severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) proteins in mammalian cells is not completely adaptive to molecular farming. Therefore, we generated several constructs of recombinant S proteins for high expression in Nicotiana benthamiana. Intramuscular injection of N. benthamiana‐expressed Sct vaccine (NSctVac) into Balb/c mice elicited both humoral and cellular immune responses, and booster doses increased neutralizing antibody titres. In human angiotensin‐converting enzyme knock‐in mice, two doses of NSctVac induced anti‐S and neutralizing antibodies, which cross‐neutralized Alpha, Beta, Delta and Omicron variants. Survival rates after lethal challenge with SARS‐CoV‐2 were up to 80%, without significant body weight loss, and viral titres in lung tissue fell rapidly, with no infectious virus detectable at 7‐day post‐infection. Thus, plant‐derived NSctVac could be a candidate COVID‐19 vaccine. [ABSTRACT FROM AUTHOR]

Parasites can exert strong selective pressures on their hosts and influence the evolution of host immunity. While several studies have examined the genetic basis for parasite resistance, the role of epigenetics in the immune response to parasites is less understood. Yet, epigenetic modifications, such as changes in DNA methylation, may allow species to respond rapidly to parasite prevalence or virulence. To test the role of DNA methylation in relation to parasite infection, we examined genome‐wide DNA methylation before and during infection by a parasitic nematode, Syngamus trachea, in a natural population of house sparrows (Passer domesticus) using reduced representation bisulfite sequencing (RRBS). We found that DNA methylation levels were slightly lower in infected house sparrows, and we identified candidate genes relating to the initial immune response, activation of innate and adaptive immunity, and mucus membrane functional integrity that were differentially methylated between infected and control birds. Subsequently, we used methylation‐sensitive high‐resolution melting (MS‐HRM) analyses to verify the relationship between methylation proportion and S. trachea infection status at two candidate genes in a larger sample dataset. We found that methylation level at NR1D1, but not CLDN22, remained related to infection status and that juvenile recruitment probability was positively related to methylation level at NR1D1. This underscores the importance of performing follow‐up studies on candidate genes. Our findings demonstrate that plasticity in the immune response to parasites can be epigenetically mediated and highlight the potential for epigenetic studies in natural populations to provide further mechanistic insight into host–parasite interactions. [ABSTRACT FROM AUTHOR]

To better understand the epidemiology of SARS‐CoV‐2 reinfections, we analyzed national data from South Korean who were followed longitudinally from January 2020 to April 2022. We conducted a nationwide retrospective cohort study to estimate possible SARS‐CoV‐2 reinfection rates in all residents in South Korea, with at least two episodes of laboratory‐confirmed SARS‐CoV‐2 infection by reverse‐transcriptase polymerase chain reaction or rapid antigen test (RAT) performed at least 45 or more days between both episodes, between January 2020 and April 2022. There were 16 130 855 laboratory‐confirmed SARS‐CoV‐2 cases in South Korea, with 55 841 (346.2 per 100 000; or 0.3% of all infections) cases of possible reinfections. The reinfection rate has increased from 6.0 cases per 100 000 during Pre‐Delta period to 128.0 cases per 100 000 and 355.1 cases per 100 000 during Delta and Omicron periods, respectively. Persons with one dose of vaccination had the highest reinfection rate of 642.2 per 100 000, followed by unvaccinated persons (536.2/100 000) and two‐dose vaccinated persons (406.3/100 000). Our finding suggests that the majority of possible reinfections occurred following the emergence of new variants. [ABSTRACT FROM AUTHOR]

With the global prevalence of COVID‐19 and the constant emergence of viral variants, boosters for COVID‐19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20–74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID‐19 vaccine at 0, 1, and 7 months. Vaccine‐induced virus‐specific antibody levels (SARS‐COV‐2‐IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS‐CoV‐2‐IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS‐CoV‐2‐IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment. [ABSTRACT FROM AUTHOR]

Aberrant expression of members of the proteasome subunit beta (PSMB) family (including PSMB2, PSMB4, PSMB7 and PSMB8) has been reported in hepatocellular carcinoma (HCC). However the role of PSMB5 in HCC is unclear. To address this issue, we examined the expression of PSMB5 in HCC tissues using the The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus databases. A quantitative real‐time PCR and immunohistochemistry were performed to validate the expression of PSMB5 in HCC. The survival mutation status and immune cell infiltration of PSMB5 were also evaluated in HCC. We then examined the effect of knocking down PSMB5 expression through RNA interference in the HCC cell line Huh7. High expression of PSMB5 was observed in HCC tissues and was associated with poor prognosis. PSMB5 expression and clinical characteristics were then incorporated to build a prognostic nomogram. We observed that PSMB5 expression was closely related to the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cell macrophages and neutrophils. Moreover silencing of PSMB5 in Huh7 significantly suppressed cell proliferation and migration at the same time as increasing apoptosis. Inhibition of the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin pathway was observed after PSMB5 downregulation in Huh7 cells. Our findings suggest that PSMB5 may promote the proliferation of HCC cells by inactivating the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin signaling pathway and thus PSMB5 may have potential as a biomarker for diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]

Little is known about risk factors for progression of high‐grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population‐based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985‐2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry and the Danish HIV Cohort Study for information on autoimmune disease, genital warts and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis and sex. The study population comprised 1222 individuals with AIN3 contributing 12 824 person‐years of follow‐up. Ninety‐seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared to individuals without these conditions. People living with HIV had a higher progression rate than HIV‐negative individuals (HR = 4.25; 95% CI: 1.87‐9.65) with the highest progression rate among those with CD4 count ≤200 cells/μL. These associations may be caused by an interplay between HPV infection and immunosuppression. [ABSTRACT FROM AUTHOR]

Objective: To assess awareness and risk of Q fever among agricultural show attendees. Setting: University of New England's Farm of the Future Pavilion, 2019, Sydney Royal Agricultural Show. Participants: Participants were ≥18 years, fluent in English, Australian residents, and gave their informed consent. Main Outcome Measures: Participants reported whether they had ever heard of Q fever and then completed the 'Q Tool' (www.qfevertool.com), which was used to assess participants' demographics and risk profiles. Cross‐tabulations and logistic regression analyses were used to examine the relationship between these factors. Results: A total of 344 participants were recruited who, in general, lived in major NSW cities and were aged 40–59 years. 62% were aware of Q fever. Living in regional/remote areas and regular contact with livestock, farms, abattoirs and/or feedlots increased the likelihood of Q fever awareness. Direct or indirect contact with feral animals was not associated with Q fever awareness after controlling for the latter risk factors. 40% of participants had a high, 21% a medium, and 30% a low risk of exposure. Slightly less than 10% reported a likely existing immunity or vaccination against Q fever. Among those who were not immune, living in a regional or remote area and Q fever awareness were independently associated with increased likelihood of exposure. Conclusions: Awareness of Q fever was relatively high. Although 61% of participants had a moderate to high risk of exposure to Q fever, they had not been vaccinated. This highlights the need to explore barriers to vaccination including accessibility of providers and associated cost. [ABSTRACT FROM AUTHOR]

Purpose: Antimicrobial stewardship programs (ASPs) are essential entities that promote the appropriate use of antimicrobials, leading to improved patient outcomes and reduced resistance. Application to the immunocompromised host is a natural progression for expansion. Cytomegalovirus (CMV) infection is a common complication following solid organ transplant with significant implications on graft survival, making it an attractive ASP target. The aim of this piece is to review our center‐specific experience with the development, implementation, and maintenance of a CMV stewardship initiative at a large transplant center. Methods: Our CMV stewardship initiative began in 2018. Herein, we review 3 years' experience and quality‐related improvement that occurred from initiation to present state and share our stewardship algorithms. Special attention is paid to the impact of the program as well as our increased understanding of the complex interplay between prevention, treatment, and host development of CMV‐specific cell‐mediated immunity (CMI). Results: We found our stewardship initiative not only reduced the incidence of ganciclovir resistance but also streamlined care via a centralized and structured approach. This objective, protocolized program has resulted in a significant shift away from a reactive to a proactive state and in turn, reduced CMV treatment rates (26% at initiation to 12% in the current state, p =.012). Conclusion: A dedicated multidisciplinary team focused on CMV stewardship is imperative in providing a patient‐centered approach focused on development of CMV‐specific CMI, and as a result prevention of CMV disease. We believe these programs will be the new gold standard for CMV management. [ABSTRACT FROM AUTHOR]

Aim: The clinical efficacy of chemoradiotherapy (CRT) is largely dependent on host immune status. The aim of this study was to identify possible markers expressed on circulating mononuclear cells to predict tumour response in patients with locally advanced rectal cancer (LARC). Methods: Peripheral blood samples were obtained from 47 patients diagnosed with LARC before and after CRT. The numbers of lymphocytes and monocyte subsets were analysed using flow cytometry. Based on clinical and pathological findings, patients were classified as high or low responders. Results: Lymphocyte counts were markedly decreased after CRT. Total numbers of lymphocytes (p = 0.030) and CD4(+) T cells (p = 0.041) in post‐CRT samples were significantly lower in low responders than in high responders. In contrast, monocyte counts were not reduced and the number of CD14dim(+) CD16(+) nonclassical (patrolling) monocytes were somewhat increased after CRT (p = 0.050). Moreover, the ratios of programmed cell death ligand 1 (PD‐L1) (+) cells on patrolling monocytes before and after CRT were significantly higher in low responders than in high responders (p = 0.0046, p = 0.0006). The same trend was observed for classical and intermediate monocytes. The expression of PD‐L1 on patrolling monocytes before CRT correlated inversely with the number of T cells and natural killer (NK) cells after CRT. PD‐L1(+) ratio in patrolling monocytes was an independent predictor for response to CRT. Conclusion: Programmed cell death ligand 1 (PD‐L1) expression on patrolling monocytes suppresses cell‐mediated immunity in patients receiving CRT which could be related to tumour response, and may be a useful biomarker for decision‐making in the management of patients with LARC. [ABSTRACT FROM AUTHOR]

Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross‐pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe‐derived products such as heat‐inactivated Mycobacterium bovis or with the glycan α‐Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non‐specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host–pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM‐mediated mechanisms in pathogen–host interactions. [ABSTRACT FROM AUTHOR]

The objective of this cohort study was to assess the relationship between perinatal calf management practices relevant to the control of paratuberculosis and passive transfer of immunoglobulin in calves born in an endemically infected Irish dairy herd. Data from 176 calves were used to assess the effect of time spent in the calving area, individual versus nondesignated calving and colostrum pasteurisation on serum total protein, zinc sulphate turbidity, globulin and γ-glutamyltransferase. In addition, the effects of colostrum quality, volume of colostrum fed, method of colostrum administration and calving season on passive transfer were quantified. Serum samples were collected as part of routine herd health monitoring from calves aged between one and seven days. Multivariate linear and logistic regression models were used to assess the effect of each variable on the test result and failure of passive transfer as determined using a cut-off point for each diagnostic test. Colostrum pasteurisation and calving area were not significantly associated with passive transfer, whereas increased time spent in the calving pen was consistently associated with a detrimental effect. In addition, a strong seasonal effect was apparent, which appeared to be unrelated to colostrum quality and calf management. The authors are unaware of published studies documenting such a significant seasonal effect on passive transfer. [ABSTRACT FROM AUTHOR]

The article focuses on purification and characterization of atopic allergens. In the past two decades, several atopic allergens, which induce IgE antibody-mediated immediate hypersensitivity in man have been purified to near homogeneity and studied for their immunochemical properties. In this paper will be reviewed some of the general findings drawn from such studies. Allergen characterization studies with extracts from these sources have confirmed the views of allergists that all extracts are multi-allergen systems and that individuals can have varying patterns of sensitivity to different allergens.

Afterward, N SB 52-59 sb -specific T cells were fluorescence-activated cell sorting-based isolated from the spleen and transferred to new hosts bearing the CD45.2 genetic marker, to facilitate discrimination between transferred antigen-specific T cells and I de novo i -generated host antigen-specific T cells. Keywords: adaptive immunity; immune memory; memory T-cell; T-cell EN adaptive immunity immune memory memory T-cell T-cell 374 376 3 05/03/23 20230501 NES 230501 T-cell memory is considered long-lasting, but new evidence recently published in I Nature i by Soerens I et al i . shows that, under certain conditions, mouse memory T-cell immunity can span several mouse lifetimes. Age is just a number: long-lasting T-cell immunity can span several lifetimes. [Extracted from the article]

Summary: Histone acetylation is a critical epigenetic modification that regulates plant immunity. Fungal pathogens secrete effectors that modulate host immunity and facilitate infection, but whether fungal pathogens have evolved effectors that directly target plant histone acetylation remains unknown.Here, we identified a secreted protein, UvSec117, from the rice false smut fungus, Ustilaginoidea virens, as a key effector that can target the rice histone deacetylase OsHDA701 and negatively regulates rice broad‐spectrum resistance against rice pathogens. UvSec117 disrupts host immunity by recruiting OsHDA701 to the nucleus and enhancing OsHDA701‐modulated deacetylation, thereby reducing histone H3K9 acetylation levels in rice plants and interfering with defense gene activation.Host‐induced gene silencing of UvSec117 promotes rice resistance to U. virens, thus providing an alternative way for developing rice false smut‐resistant plants.This is the first direct evidence demonstrating that a fungal effector targets a histone deacetylase to suppress plant immunity. Our data provided insight into a counter‐defense mechanism in a plant pathogen that inactivates host defense responses at the epigenetic level. [ABSTRACT FROM AUTHOR]

Periodontal disease refers to inflammation of the tissues that support the tooth. It is of multifactorial etiology. Innate and adaptive immune cells participate jointly through the release of their molecules and mechanisms of action in order to maintain homeostasis in periodontal tissues, so the host's immune response plays an essential role in defense against microorganisms. However, bacterial persistence and the dysregulation of the immune system as an exaggerated response can lead to the worsening of periodontal disease, leading to loss of gingival tissue and alveolar bone and thereby loss of teeth. Therefore, a better understanding of the cellular mechanisms involved in the development of periodontal disease is necessary to design new treatments and prophylactic measures in order to decrease the prevalence of this disease that afflicts a large part of the world population. [ABSTRACT FROM AUTHOR]

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease‐19 (COVID‐19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID‐19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID‐19 or severe acute respiratory syndrome coronavirus‐2 (SARS‐COV‐2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID‐19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll‐like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID‐19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID‐19 disease severity. Understanding host immune gene variations associated with the SARS‐COV‐2 infection opens insights to control the pathophysiology of emerging viral infections. [ABSTRACT FROM AUTHOR]

Background: Vaccine preventable illnesses are important sources of morbidity, mortality, and increased healthcare costs in pediatric LT recipients. Our aim was to measure the seroprevalence of antibodies to measles and VZV in this population. Methods: We conducted a retrospective chart review of 44 patients who received LT before age 18 at UCLA Mattel Children's Hospital from January 2008 to December 2017. Results: Median age at transplantation was 2.5 years (IQR 1.2–7.7). Post‐transplant measles antibodies were present in 17 of 37 patients (46%); risk factors for seronegativity included younger age at transplant (p =.02) and greater time from transplant to testing (p =.04). Post‐transplant VZV antibodies were present in 17 of 39 patients (44%); risk factors for seronegativity included greater time from transplant to testing (p =.04). 6 of 16 patients (38%) who tested positive for pre‐transplant VZV antibodies tested negative after transplantation. Fourteen of 20 patients (70%) with at least 1 documented dose of the MMR vaccine tested positive for post‐transplant measles antibodies. Ten of 20 of patients (50%) with at least 1 documented dose of the VZV vaccine tested positive for post‐transplant VZV antibodies. We also describe 10 patients who received post‐transplant measles and VZV vaccines without documented complications. Conclusions: Our study suggests that pediatric LT patients are at greater risk of contracting measles and VZV despite vaccination status, and that prevalence of measles and VZV antibodies decreases as time from transplantation increases. This should weigh into the institutional risk–benefit assessment when deciding whether or not to administer LAVs to these patients. [ABSTRACT FROM AUTHOR]

Immunotherapy has revolutionized cancer therapy by reactivating tumour‐resident cytotoxic lymphocytes. More recently, immunotherapy has emerged to restore immunity against infectious agents, including bacterial infections. Immunotherapy primarily targets inhibitory pathways in T cells, however interest in other effector populations, such as natural killer (NK) cells, is growing. We have previously discovered that NK cell metabolism, proliferation and activation can be neutralized through the immunosuppressive transforming growth factor (TGF)‐β pathway by inducing plasticity of NK cells and differentiation into innate lymphoid cell (ILC)1‐like subsets. NK cells are also regulated through cytokine‐inducible SH2‐containing protein (CIS), which is induced by interleukin (IL)‐15 and is a potent intracellular checkpoint suppressing NK cell survival and function. Targeting these two distinct pathways to restore NK cell function has shown promise in cancer models, but their application in bacterial infection remains unknown. Here, we investigate whether enhancement of NK cell function can improve anti‐bacterial immunity, using Salmonella Typhimurium as a model. We identified conversion of NK cells to ILC1‐like for the first time in the context of bacterial infection, where TGF‐β signalling contributed to this plasticity. Future study should focus on identifying further drivers of ILC1 plasticity and its functional implication in bacterial infection model. We further describe that CIS‐deficient mice displayed enhanced pro‐inflammatory function and dramatically enhanced anti‐bacterial immunity. Inhibition of CIS may present as a viable therapeutic option to enhance immunity towards bacterial infection. [ABSTRACT FROM AUTHOR]

The enactment of the Covert Human Intelligence Sources (Criminal Conduct) Act 2021 pre‐empted the outcome of the appeal against the decision of the Investigatory Powers Tribunal in the so‐called 'third direction' case. This legislation article considers the background to the statute in the form both of the (absence of a) legal regime governing informant participation in criminality as revealed by reviews of events within the Northern Irish Troubles and the recent litigation. It analyses the key legal issues raised by the Act and locates it within the modern project of rationalising the law related to national security. [ABSTRACT FROM AUTHOR]

During the growth season, northern forests in Sweden daily receive more hours of far‐red (FR)‐enriched light or twilight (shade) as compared to southern forests. Norway spruce (shade‐tolerant) are adapted to latitudinal variation in twilight characterized by a northward increase in FR requirement to maintain growth. Shade is a stressful condition that affects plant growth and increases plant's susceptibility to pathogen attack. Lignin plays a central role in plant defense and its metabolism is regulated by light wavelength composition (light quality). In the current work, we studied regulation of lignin synthesis and defense‐related genes (growth‐defense trade‐offs) in response to shade in Norway spruce. In most angiosperms, light promotes lignin synthesis, whereas shade decreases lignin production leading to weaker stem, which may make plants more disease susceptible. In contrast, enhanced lignin synthesis was detected in response to shade in Norway spruce. We detected a higher number of immunity/defense‐related genes up‐regulated in northern populations as compared to south ones in response to shade. Enhanced lignin synthesis coupled with higher defense‐related gene expression can be interpreted as an adaptive strategy for better survival in northern populations. Findings will contribute to ensuring deployment of well‐adapted genetic material and identifying tree families with enhanced disease resistance. Enhanced lignin synthesis was detected in Norway spruce under shade in contrast to angiosperms. Shade also revealed ecotypic variation in defense‐related gene expression in Norway spruce. [ABSTRACT FROM AUTHOR]

Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis. Synopsis: IBD (both CD and UC) is characterized by dysbiosis and altered immune pathways that lead to and sustain prolonged inflammation in the gut. As IgA are the main drivers of commensal selection in the healthy gut, this study aimed at assessing subclass‐related structure and functions of IgA in both CD and UC. Evidence of a chain of subclass‐dependent functional disparities between CD and UC IgAs affecting antibody glycosylation, transport across epithelia, and affinity, which may interfere in optimal commensal selection to promote dysbiosisWhile only IgA2 could undergo RT in non‐IBD, IgA1 in CD had the ability to do so and neither IgA1 nor IgA2 were able to in UC.Despite predominant dual IgA1 and IgA2 binding on stool microbiota, CD associates with enriched commensal binding in the IgA1+ fraction, and UC with a marked reduction in IgA overall reactivity [ABSTRACT FROM AUTHOR]

Cyclic GMP‐AMP synthase (cGAS) and stimulator of interferon genes (STING) play critical roles in the innate immunity against infectious diseases and are required to link pathogen DNA sensing to immune responses. However, the mechanisms by which cGAS‐STING‐induced cytokines suppress the adaptive immune response against malaria infections remain poorly understood. Here, cGAS‐STING signaling is identified to play a detrimental role in regulating anti‐malaria immunity. cGAS or STING deficiency in mice markedly prolongs mouse survival during lethal malaria Plasmodium yoelii nigeriensis N67C infections by reducing late interleukin (IL)‐6 production. Mechanistically, cGAS/STING recruits myeloid differentiation factor 88 (MyD88) and specifically induces the p38‐dependent signaling pathway for late IL‐6 production, which, in turn, expands CD11b+Ly6Chi proinflammatory monocytes to inhibit immunity. Moreover, the blockage or ablation of the cGAS‐STING‐MyD88‐p38‐IL‐6 signaling axis or the depletion of CD11b+Ly6Chi proinflammatory monocytes provides mice a significant survival benefit during N67C and other lethal malaria‐strain infections. Taken together, these findings identify a previously unrecognized detrimental role of cGAS‐STING‐MyD88‐p38 axis in infectious diseases through triggering the late IL‐6 production and proinflammatory monocyte expansion and provide insight into how targeting the DNA sensing pathway, dysregulated cytokines, and proinflammatory monocytes enhances immunity against infection. [ABSTRACT FROM AUTHOR]

Summary: Plants encode > 100 metalloproteases representing > 19 different protein families. Tools to study this large and diverse class of proteases have not yet been introduced into plant research.We describe the use of hydroxamate‐based photoaffinity probes to explore plant proteomes for metalloproteases.We detected labelling of 23 metalloproteases in leaf extracts of the model plant Arabidopsis thaliana that belong to nine different metalloprotease families and localize to different subcellular compartments. The probes identified several chloroplastic FtsH proteases, vacuolar aspartyl aminopeptidase DAP1, peroxisomal metalloprotease PMX16, extracellular matrix metalloproteases and many cytosolic metalloproteases. We also identified nonproteolytic metallohydrolases involved in the release of auxin and in the urea cycle. Studies on tobacco plants (Nicotiana benthamiana) infected with the bacterial plant pathogen Pseudomonas syringae uncovered the induced labelling of PRp27, a secreted protein with implicated metalloprotease activity. PRp27 overexpression increases resistance, and PRp27 mutants lacking metal binding site are no longer labelled, but still show increased immunity.Collectively, these studies reveal the power of broad‐range metalloprotease profiling in plants using hydroxamate‐based probes. [ABSTRACT FROM AUTHOR]

Problem: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre‐existing conditions that influence immune mediator changes in response to contraceptive initiation. Methods: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA‐IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. Results: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA‐IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. Conclusion: We conclude that pre‐contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response. [ABSTRACT FROM AUTHOR]