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Background: Dogs are definitive hosts of Echinococcus granulosus , with the small intestine being the only site of parasitic infections. However, the immunomodulatory processes that occur during interactions between E. granulosus and its definitive host remain unclear. Therefore, this study aimed to evaluate gene transcription patterns in canine small intestinal epithelial cells (CIECs) following stimulation by E. granulosus protoscoleces (PSCs). Particularly, this study investigated the roles of pattern recognition receptors (PRRs), involved in recognizing pathogen-associated molecular patterns (PAMPs) and mediating the host innate immune response to the tapeworm E. granulosus. Methods: RNA sequencing (RNA-seq) was used to examine gene transcription patterns in CIECs following stimulation with PSCs for 12 and 24 h. The potential roles of differentially expressed (DE) genes were inferred through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: RNA-seq analysis identified 78,206,492–90,548,214 clean reads in 12 RNA samples. This included six samples stimulated with PSCs for 12 h (PSC1_12h–PSC3_12h) and 24 h (PSC1_24h–PSC3_24h) and six corresponding control samples (PBS1_12h–PBS3_12h and PBS1_24h–PBS3_24h). In the PSC_12h vs. PBS_12h and PSC_24h vs. PBS_24h groups, 3,520 (2,359 upregulated and 1,161 downregulated) and 3,287 (1765 upregulated and 1,522 downregulated) DEgenes were identified, respectively. The expression of 45 PRRs genes was upregulated in the PSC_12h and PSC_24h groups compared to those in the control groups, including 4 Toll-like receptors (TLRs), 4C-type lectin receptors (CLRs), 3 NOD-like receptors (NLRs), 17 G protein-coupled receptors (GPCRs), 4 scavenger receptors (SRs), and 13 leucine-rich repeat-containing proteins (LRRCs). GO enrichment and KEGG analyses revealed that these DEgenes were mainly involved in the regulation of host immune response processes and molecules. These included antigen processing and presentation, Th17, PI3K-Akt, Th1, and Th2 cell differentiation, neutrophil extracellular trap formation, NOD- and Toll-like receptors, TNF, intestinal immune network for IgA production and IL-17 signaling pathway. Furthermore, the identified DEgenes were involved in the regulation of signaling molecules and interaction (e.g., cell adhesion molecules and ECM-receptor interaction). Conclusion: These preliminary findings provide novel perspectives on the host innate immune response to E. granulosus PSC stimulation, with a focus on the involvement of E. granulosus -specific PRRs in host defense mechanisms against infection. [ABSTRACT FROM AUTHOR]

Innate immunity is the first line of defense against infections and the only known available strategy for invertebrates. Crustaceans, being mostly aquatic invertebrates, are constantly exposed to potential pathogens in the surrounding water. Their immune system abolishes most microbes that enter and are recognized as a threat. However, the stress produced by high population densities and abiotic changes, in aquaculture, disrupts the host-pathogen balance, leading to severe economic losses in this industry. Consequently, crustacean immunology has become a prime area of research where significant progress has been made. This review provides our current understanding of the key pattern recognition receptors in crustaceans, with special focus on Decapoda, and their roles in triggering an immune response. We discuss recent developments in the field of signal transduction pathways such as Toll-like receptors (TLRs) and the immune deficiency (IMD) pathway, and examine the role of antimicrobial peptides (AMPs) in pathogen defense. Additionally, we analyze how environmental stressors—such as temperature fluctuations, ammonia levels, and pollution—impact immune responses and increase susceptibility to diseases. Finally, we highlight future research directions, emphasizing the need to explore the interactions between environmental stressors and immune signaling pathways and to develop strategies to enhance immune responses in crustaceans within aquaculture settings. Altogether, these advancements deepen our understanding of pathogen recognition in invertebrates and the specific defense mechanisms employed by crustaceans, particularly in response to infections triggered by pathogens under abiotic stressors. [ABSTRACT FROM AUTHOR]

Abstract Viral infections pose significant threats to human health, leading to a diverse spectrum of infectious diseases. The innate immune system serves as the primary barrier against viruses and bacteria in the early stages of infection. A rapid and forceful antiviral innate immune response is triggered by distinguishing between self-nucleic acids and viral nucleic acids. RNA-binding proteins (RBPs) are a diverse group of proteins which contain specific structural motifs or domains for binding RNA molecules. In the last decade, numerous of studies have outlined that RBPs influence viral replication via diverse mechanisms, directly recognizing viral nucleic acids and modulating the activity of pattern recognition receptors (PRRs). In this review, we summarize the functions of RBPs in regulation of host-virus interplay by controlling the activation of PRRs, such as RIG-I, MDA5, cGAS and TLR3. RBPs are instrumental in facilitating the identification of viral RNA or DNA, as well as viral structural proteins within the cellular cytoplasm and nucleus, functioning as co-receptor elements. On the other hand, RBPs are capable of orchestrating the activation of PRRs and facilitating the transmission of antiviral signals to downstream adaptor proteins by post-translational modifications or aggregation. Gaining a deeper comprehension of the interaction between the host and viruses is crucial for the development of novel therapeutics targeting viral infections.

Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)‐mediated inflammation, including upregulation of various transcription factors and the activation of pro‐inflammatory pathways important for immune surveillance. Dysfunction of PRRs‐mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs‐driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure‐based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll‐like Receptor 4 (TLR4). Taking advantage of an exo‐anomeric conformation and specific molecular shape of synthetic nonreducing β,β‐diglucosamine, which was investigated by NMR, we developed two sets of lipid A mimicking glycolipids capable of either potently activating innate immune responses or inhibiting pro‐inflammatory signaling. Stereoselective 1,1′‐glycosylation towards fully orthogonally protected nonreducing GlcNβ(1↔1′)βGlcN followed by stepwise assembly of differently functionalised phosphorylated glycolipids provided biologically active molecules that were evaluated for their ability to trigger or to inhibit cellular innate immune responses. Two LPS mimetics, identified as potent TLR4‐specific inducers of the intracellular signaling pathways, serve as vaccine adjuvant‐ and immunotherapy candidates, while anionic glycolipids with TLR4‐inhibitory potential hold therapeutic promise for the management of acute or chronic inflammation. [ABSTRACT FROM AUTHOR]

Viral infections pose significant threats to human health, leading to a diverse spectrum of infectious diseases. The innate immune system serves as the primary barrier against viruses and bacteria in the early stages of infection. A rapid and forceful antiviral innate immune response is triggered by distinguishing between self-nucleic acids and viral nucleic acids. RNA-binding proteins (RBPs) are a diverse group of proteins which contain specific structural motifs or domains for binding RNA molecules. In the last decade, numerous of studies have outlined that RBPs influence viral replication via diverse mechanisms, directly recognizing viral nucleic acids and modulating the activity of pattern recognition receptors (PRRs). In this review, we summarize the functions of RBPs in regulation of host-virus interplay by controlling the activation of PRRs, such as RIG-I, MDA5, cGAS and TLR3. RBPs are instrumental in facilitating the identification of viral RNA or DNA, as well as viral structural proteins within the cellular cytoplasm and nucleus, functioning as co-receptor elements. On the other hand, RBPs are capable of orchestrating the activation of PRRs and facilitating the transmission of antiviral signals to downstream adaptor proteins by post-translational modifications or aggregation. Gaining a deeper comprehension of the interaction between the host and viruses is crucial for the development of novel therapeutics targeting viral infections. [ABSTRACT FROM AUTHOR]

BackgroundDogs are definitive hosts of Echinococcus granulosus, with the small intestine being the only site of parasitic infections. However, the immunomodulatory processes that occur during interactions between E. granulosus and its definitive host remain unclear. Therefore, this study aimed to evaluate gene transcription patterns in canine small intestinal epithelial cells (CIECs) following stimulation by E. granulosus protoscoleces (PSCs). Particularly, this study investigated the roles of pattern recognition receptors (PRRs), involved in recognizing pathogen-associated molecular patterns (PAMPs) and mediating the host innate immune response to the tapeworm E. granulosus.MethodsRNA sequencing (RNA-seq) was used to examine gene transcription patterns in CIECs following stimulation with PSCs for 12 and 24 h. The potential roles of differentially expressed (DE) genes were inferred through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsRNA-seq analysis identified 78,206,492–90,548,214 clean reads in 12 RNA samples. This included six samples stimulated with PSCs for 12 h (PSC1_12h–PSC3_12h) and 24 h (PSC1_24h–PSC3_24h) and six corresponding control samples (PBS1_12h–PBS3_12h and PBS1_24h–PBS3_24h). In the PSC_12h vs. PBS_12h and PSC_24h vs. PBS_24h groups, 3,520 (2,359 upregulated and 1,161 downregulated) and 3,287 (1765 upregulated and 1,522 downregulated) DEgenes were identified, respectively. The expression of 45 PRRs genes was upregulated in the PSC_12h and PSC_24h groups compared to those in the control groups, including 4 Toll-like receptors (TLRs), 4C-type lectin receptors (CLRs), 3 NOD-like receptors (NLRs), 17 G protein-coupled receptors (GPCRs), 4 scavenger receptors (SRs), and 13 leucine-rich repeat-containing proteins (LRRCs). GO enrichment and KEGG analyses revealed that these DEgenes were mainly involved in the regulation of host immune response processes and molecules. These included antigen processing and presentation, Th17, PI3K-Akt, Th1, and Th2 cell differentiation, neutrophil extracellular trap formation, NOD- and Toll-like receptors, TNF, intestinal immune network for IgA production and IL-17 signaling pathway. Furthermore, the identified DEgenes were involved in the regulation of signaling molecules and interaction (e.g., cell adhesion molecules and ECM-receptor interaction).ConclusionThese preliminary findings provide novel perspectives on the host innate immune response to E. granulosus PSC stimulation, with a focus on the involvement of E. granulosus-specific PRRs in host defense mechanisms against infection.

Innate immunity is the first line of defense against infections and the only known available strategy for invertebrates. Crustaceans, being mostly aquatic invertebrates, are constantly exposed to potential pathogens in the surrounding water. Their immune system abolishes most microbes that enter and are recognized as a threat. However, the stress produced by high population densities and abiotic changes, in aquaculture, disrupts the host-pathogen balance, leading to severe economic losses in this industry. Consequently, crustacean immunology has become a prime area of research where significant progress has been made. This review provides our current understanding of the key pattern recognition receptors in crustaceans, with special focus on Decapoda, and their roles in triggering an immune response. We discuss recent developments in the field of signal transduction pathways such as Toll-like receptors (TLRs) and the immune deficiency (IMD) pathway, and examine the role of antimicrobial peptides (AMPs) in pathogen defense. Additionally, we analyze how environmental stressors—such as temperature fluctuations, ammonia levels, and pollution—impact immune responses and increase susceptibility to diseases. Finally, we highlight future research directions, emphasizing the need to explore the interactions between environmental stressors and immune signaling pathways and to develop strategies to enhance immune responses in crustaceans within aquaculture settings. Altogether, these advancements deepen our understanding of pathogen recognition in invertebrates and the specific defense mechanisms employed by crustaceans, particularly in response to infections triggered by pathogens under abiotic stressors.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co‐operators of oncogenic KRAS in the lung remains ill‐defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent‐in‐melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS‐addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine‐derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome‐associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK‐induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D‐driven LAC in both hematopoietic (immune) and non‐hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2‐deficient mice is associated with unaltered protein levels of mature Caspase‐1 and IL‐1β inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D‐driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase‐1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor‐promoting role, independent of inflammasomes, in mutant KRAS‐addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These disorders include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorders, headaches, and epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted the role of immunity and neuroinflammation in neuropsychiatric disorders. Toll‐like receptors (TLRs) are innate receptors that act as a bridge between the innate and adaptive immune systems via adaptor proteins (e.g., MYD88) and downstream elements; TLRs are classified into 13 families that are involved in normal function and illnesses of the CNS. TLRs expression affects the course of neuropsychiatric disorders, and is influenced during their pharmacotherapy; For example, the expression of multiple TLRs is normalized during the major depressive disorder pharmacotherapy. Here, the role of TLRs in neuroimmunology, treatment, and management of neuropsychiatric disorders is discussed. We recommend longitudinal studies to comparatively assess the cell‐type‐specific expression of TLRs during treatment, illness progression, and remission. Also, further research should explore molecular insights into TLRs regulation and related pathways. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naïve T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum increased toll-like receptor 4 gene expression in synergy with nuclear factor κB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, L. amazonensis induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8+ T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies. [ABSTRACT FROM AUTHOR]

Our understanding of the specificities of innate immune protection against viral pathogens in non-model invertebrate species is limited, and comparative immunological approaches may offer opportunities to protect aquaculturally significant species such as abalone, against viral threats. Haliotid herpesvirus (HaHV-1) is a re-emerging viral pathogen of abalone, and has a high mortality rate in the dominant wild and farmed species in Australia, the Australian greenlip abalone (Haliotis laevigata), the blacklip (Haliotis rubra) and a hybrid of the two. To gain a better understanding of the anti-viral immune system counterparts of Australian abalone, gene mining strategies and domain analysis of the recently released H. laevigata draft genome was performed, with comparisons made to the better studied mollusc, the oyster (Crassostrea gigas). Significant divergence in members of the TLR, cytosolic RNA/DNA and RNA interference signalling pathways was observed between the two molluscs, with the oyster more closely reflecting that of the mammalian immune response. Interestingly, a homolog for the anti-viral RNA sensing adaptor protein Mitochondrial anti-viral-signalling protein was absent in H. laevigata, as well as the 4 other abalone protein databases currently available, despite the presence of a RIG-I homolog. Additionally, STING, a member of the dsDNA sensing pathway was absent in H. laevigata, as well as 2 other abalone species, however is present in the oyster genome, and two additional abalone species (Haliotis rufescens, Haliotis discus hannai).This work provides a better understanding of the key features of the abalone anti-viral innate immune signalling system and may provide much needed information towards the development of anti-viral strategies in these animals.

Breast cancer stands as a primary malignancy among women, ranking second in global cancer-related deaths. Despite treatment advancements, many patients progress to metastatic stages, posing a significant therapeutic challenge. Current therapies primarily target cancer cells, overlooking their intricate interactions with the tumor microenvironment (TME) that fuel progression and treatment resistance. Dysregulated innate immunity in breast cancer triggers chronic inflammation, fostering cancer development and therapy resistance. Innate immune pattern recognition receptors (PRRs) have emerged as crucial regulators of the immune response as well as of several immune-mediated or cancer cell-intrinsic mechanisms that either inhibit or promote tumor progression. In particular, several studies showed that the Toll-like receptor 2 (TLR2) and the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathways play a central role in breast cancer progression. In this review, we present a comprehensive overview of the role of TLR2 and STING in breast cancer, and we explore the potential to target these PRRs for drug development. This information will significantly impact the scientific discussion on the use of PRR agonists or inhibitors in cancer therapy, opening up new and promising avenues for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Crustacean species are among the most valued seafood with socioeconomic and ecological implications in the global fisheries sector. Microbial infections to the farming stock due to continued expansion and aquaculture puts global crustacean production at risk. Understanding and reviewing the complex innate immune system of crustaceans would be pivotal in formulating informed decisions for the control and management of epidemic diseases, thus making the global crustacean aquaculture industry sustainable. Under the purview of innate immunity in crustaceans, pattern recognition receptors (PRRs) represent the sensors capable of discriminating non‐self pathogenic modules and invoking the activation of immune responses. The immunity to infections can be manifested at cellular (via phagocytosis, apoptosis, nodulation and encapsulation) and humoral (effected by prophenoloxidase cascade, lectins, antimicrobial proteins) levels leading to the elimination of pathogens or subversion of the pathogenic implications. In this review, we discuss the participatory role of 12 types of PRRs identified from crustacean species with an exhaustive focus on structural and functional specificities in binding to pathogens and possible execution of the immune activity. Moreover, we have elaborated on the PRRs‐associated or possible signalling cascades (Toll‐NFκB, IMD‐NFκB and JAK‐STAT) in crustacean species that could bridge our understanding of the resistance or susceptibility of the host to varied pathogenic infections thus providing clues to the regulatory mechanisms involved in pathogenesis of infectious diseases and mechanisms of immunity. [ABSTRACT FROM AUTHOR]

Fibrinogen-related proteins (FREPs) are calcium-dependent lectins with one fibrinogen domain and one or two immunoglobulin-like domains. The FREPs of gastropod molluscs can undergo somatic diversification, which is unique among pathogen-recognizing molecules of invertebrates. The structure of the genomic regions encoding FREPs implies the possibility of alternative splicing and somatic mutagenesis. Since the discovery of FREPs in Biomphalaria glabrata, these molecules have been described in many gastropods. At least 14 subfamilies of FREPs are currently known. FREPs of different subfamilies selectively participate in the immune response to various pathogens. In particular, their role in defense reactions to trematode invasion and resistance to trematodes of particular species has been confirmed. The supposed functions of FREPs are diverse, ranging from the recognition of foreign matter to the opsonization and neutralization of pathogens. Despite the abundance of studies of FREPs, the Russian literature on this subject is scarce. The main purpose of this review is to analyze the available information on gastropod FREPs and to discuss their role among pattern recognition receptors of molluscs. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a significant global health challenge, claiming the lives of up to 1.5 million individuals annually. TB is caused by the human pathogen Mycobacterium tuberculosis (Mtb), which primarily infects innate immune cells in the lungs. These immune cells play a critical role in the host defense against Mtb infection, influencing the inflammatory environment in the lungs, and facilitating the development of adaptive immunity. However, Mtb exploits and manipulates innate immune cells, using them as favorable niche for replication. Unfortunately, our understanding of the early interactions between Mtb and innate effector cells remains limited. This review underscores the interactions between Mtb and various innate immune cells, such as macrophages, dendritic cells, granulocytes, NK cells, innate lymphocytes-iNKT and ILCs. In addition, the contribution of alveolar epithelial cell and endothelial cells that constitutes the mucosal barrier in TB immunity will be discussed. Gaining insights into the early cellular basis of immune reactions to Mtb infection is crucial for our understanding of Mtb resistance and disease tolerance mechanisms. We argue that a better understanding of the early host-pathogen interactions could inform on future vaccination approaches and devise intervention strategies. [ABSTRACT FROM AUTHOR]

The innate immune system is critical for inducing durable and protective T cell responses to infection and has been increasingly recognized as a target for cancer immunotherapy. In this review, we present a framework wherein distinct innate immune signaling pathways activate five key dendritic cell activities that are important for T cell-mediated immunity. We discuss molecular pathways that can agonize these activities and highlight that no single pathway can agonize all activities needed for durable immunity. The immunological distinctions between innate immunotherapy administration to the tumor microenvironment versus administration via vaccination are examined, with particular focus on the strategies that enhance dendritic cell migration, interferon expression, and interleukin-1 family cytokine production. In this context, we argue for the importance of appreciating necessity vs. sufficiency when considering the impact of innate immune signaling in inflammation and protective immunity and offer a conceptual guideline for the development of efficacious cancer immunotherapies. Innate immune pathways are commonly discussed targets of cancer immunotherapy. Cao and Kagan review the state of this rapidly advancing field of study. They introduce the concept that five key innate immune activities in dendritic cells are needed to stimulate durable T cell-mediated anti-tumor immunity. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cause of cancer worldwide and is the leading cause of mortality for women across most of the world. Immunotherapy is a burgeoning area of cancer treatment, including for breast cancer; these are therapies that harness the power of the immune system to clear cancerous cells. Toll-like receptor 3 (TLR3) is an RNA receptor found in the endosome, and ligands that bind to TLR3 are currently being tested for their efficacy as breast cancer immunotherapeutics. The current review introduces TLR3 and the role of this receptor in breast cancer, and summarizes data on the potential use of TLR3 ligands, mainly polyinosinic:polycytidylic acid and its derivatives, as breast cancer monot [ABSTRACT FROM AUTHOR]

Objective and backgroundPattern recognition receptors (PRRs) on immune and parenchymal cells can detect danger-associated molecular patterns (DAMPs) released from cells damaged during ischemia-reperfusion injury (IRI), in heart attack or stroke settings, but also as an unavoidable consequence of solid organ transplantation. Despite IRI being a significant clinical problem across all solid organ transplants, there are limited therapeutics and patient-specific diagnostics currently available.MethodsWe screened portal blood samples obtained from 67 human liver transplant recipients both pre- [portal vein (PV) sample] and post-(liver flush; LF) reperfusion for their ability to activate a panel of PRRs, and analyzed this reactivity in relation to biopsy-proven IRI.ResultsPV samples from IRI+ orthotopic liver transplantation (OLT) patients (n = 35) decreased activation of hTLR4- and hTLR9-transfected cells, whereas PV from IRI- patients (n = 32) primarily increased hTLR7 and hNOD2 activation. LF samples from OLT-IRI patients significantly increased activation of hTLR4 and hTLR9 over IRI- LF. In addition, the change from baseline reactivity to hTLR4/9/NOD2 was significantly higher in IRI+ than IRI- OLT patients.ConclusionsThese results demonstrate that TLR4/7/9 and NOD2 are involved in either promoting or attenuating hepatic IRI, and suggest a diagnostic screening of portal blood for reactivity to these PRRs might prove useful for prediction and/or therapeutic intervention in OLT patients before transplantation.

Innate immune receptors that form complexes with secondary receptors, activating multiple signalling pathways, modulate cellular activation and play essential roles in regulating homeostasis and immunity. We have previously identified a variety of bovine C-type lectin-like receptors that possess similar functionality than their human orthologues. Mincle (CLEC4E), a heavily glycosylated monomer, is involved in the recognition of the mycobacterial component Cord factor (trehalose 6,6′-dimycolate). Here we characterise the bovine homologue of Mincle (boMincle), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (huMincle), although there are some notable differences. In the absence of cross-reacting antibodies, boMincle-specific antibodies were created and used to demonstrate that, like the human receptor, boMincle is predominantly expressed by myeloid cells. BoMincle surface expression increases during the maturation of monocytes to macrophages. However, boMincle mRNA transcripts were also detected in granulocytes, B cells, and T cells. Finally, we show that boMincle binds to isolated bovine CD4+ T cells in a specific manner, indicating the potential to recognise endogenous ligands. This suggests that the receptor might also play a role in homeostasis in cattle. [ABSTRACT FROM AUTHOR]

Innate immune receptors that form complexes with secondary receptors, activating multiple signalling pathways, modulate cellular activation and play essential roles in regulating homeostasis and immunity. We have previously identified a variety of bovine C-type lectin-like receptors that possess similar functionality than their human orthologues. Mincle (CLEC4E), a heavily glycosylated monomer, is involved in the recognition of the mycobacterial component Cord factor (trehalose 6,6′-dimycolate). Here we characterise the bovine homologue of Mincle (boMincle), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (huMincle), although there are some notable differences. In the absence of cross-reacting antibodies, boMincle-specific antibodies were created and used to demonstrate that, like the human receptor, boMincle is predominantly expressed by myeloid cells. BoMincle surface expression increases during the maturation of monocytes to macrophages. However, boMincle mRNA transcripts were also detected in granulocytes, B cells, and T cells. Finally, we show that boMincle binds to isolated bovine CD4+ T cells in a specific manner, indicating the potential to recognise endogenous ligands. This suggests that the receptor might also play a role in homeostasis in cattle.

Eriocheir sinensis (Chinese mitten crab) is one of the main economic species in China, which has evolved an extremely sophisticated innate immune system to fend off disease invasions. However, bacterial and viral infections have caused significant financial losses for the E. sinensis aquaculture in recent years. Making well-informed judgments for the control microbial infections would require a thorough understanding and clarification of the intricate innate immune system of E. sinensis. Innate immunity is essential for the host's defense against invasive pathogens. Pattern recognition receptors (PRRs) initially recognize pathogen-associated molecular patterns (PAMPs) and trigger an innate immune response, causing the generation of inflammatory cytokine and promoting the clearance and control of pathogens. In E. sinensis , Toll/Toll-like receptors, lipopolysaccharide and β-1,3-glucan binding proteins, C-type lectins, galactoside-binding lectins, L-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified to be PRRs that are involved in the recognition of bacteria, fungi, and viruses. In this review, we give a comprehensive overview of the literature regarding PRRs' roles in the immunological defenses of E. sinensis , with the aim of providing clues to the mechanisms of innate immunity. [ABSTRACT FROM AUTHOR]

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics. [ABSTRACT FROM AUTHOR]

Innate immunity is a primary defense system against microbial infections. Innate immune pattern recognition receptors (PRRs) play pivotal roles in detection of invading pathogens. When pathogens, such as bacteria and viruses, invade our bodies, their components are recognized by PRRs as pathogen-associated molecular patterns (PAMPs), activating the innate immune system. Cellular components such as DNA and RNA, acting as damage-associated molecular patterns (DAMPs), also activate innate immunity through PRRs under certain conditions. Activation of PRRs triggers inflammatory responses, interferon-mediated antiviral responses, and the activation of acquired immunity. Research on innate immune receptors is progressing rapidly. A variety of these receptors has been identified, and their regulatory mechanisms have been elucidated. Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) constitute a major family of intracellular PRRs and are involved in not only combating pathogen invasion but also maintaining normal homeostasis. Some NLRs are known to form multi-protein complexes called inflammasomes, a process that ultimately leads to the production of inflammatory cytokines and induces pyroptosis through the proteolytic cascade. The aberrant activation of NLRs has been found to be associated with autoimmune diseases. Therefore, NLRs are considered targets for drug discovery, such as for antiviral drugs, immunostimulants, antiallergic drugs, and autoimmune disease drugs. This review summarizes our recent understanding of the activation and regulation mechanisms of NLRs, with a particular focus on their structural biology. These include NOD2, neuronal apoptosis inhibitory protein (NAIP)/NLRC4, NLR family pyrin domain containing 1 (NLRP1), NLRP3, NLRP6, and NLRP9. NLRs are involved in a variety of diseases, and their detailed activation mechanisms based on structural biology can aid in developing therapeutic agents in the future. [ABSTRACT FROM AUTHOR]

Malaria is the cause of 600.000 deaths annually. However, these deaths represent only a tiny fraction of total malaria cases. Repeated natural infections with the causative agent, Plasmodium sp. parasites, induce protection from severe disease but not sterile immunity. Thus, immunity to Plasmodium is incomplete. Conversely, immunization with attenuated sporozoite stage parasites can induce sterile immunity albeit after multiple vaccinations. These different outcomes are likely to be influenced strongly by the innate immune response to different stages of the parasite lifecycle. Even small numbers of sporozoites can induce a robust proinflammatory type I interferon response, which is believed to be driven by the sensing of parasite RNA. Moreover, induction of innate like gamma-delta cells contributes to the development of adaptive immune responses. Conversely, while blood stage parasites can induce a strong proinflammatory response, regulatory mechanisms are also triggered. In agreement with this, intact parasites are relatively weakly sensed by innate immune cells, but isolated parasite molecules, notably DNA and RNA can induce strong responses. Thus, the innate response to Plasmodium parasite likely represents a trade-off between strong pro-inflammatory responses that may potentiate immunity and regulatory processes that protect the host from cytokine storms that can induce life threatening illness. [ABSTRACT FROM AUTHOR]

Malaria is the cause of 600.000 deaths annually. However, these deaths represent only a tiny fraction of total malaria cases. Repeated natural infections with the causative agent, Plasmodium sp. parasites, induce protection from severe disease but not sterile immunity. Thus, immunity to Plasmodium is incomplete. Conversely, immunization with attenuated sporozoite stage parasites can induce sterile immunity albeit after multiple vaccinations. These different outcomes are likely to be influenced strongly by the innate immune response to different stages of the parasite lifecycle. Even small numbers of sporozoites can induce a robust proinflammatory type I interferon response, which is believed to be driven by the sensing of parasite RNA. Moreover, induction of innate like gamma-delta cells contributes to the development of adaptive immune responses. Conversely, while blood stage parasites can induce a strong proinflammatory response, regulatory mechanisms are also triggered. In agreement with this, intact parasites are relatively weakly sensed by innate immune cells, but isolated parasite molecules, notably DNA and RNA can induce strong responses. Thus, the innate response to Plasmodium parasite likely represents a trade-off between strong pro-inflammatory responses that may potentiate immunity and regulatory processes that protect the host from cytokine storms that can induce life threatening illness.

Fungal keratitis (FK) is a refractory disease that poses a serious threat to vision, with common risk factors like eye trauma, contact lens wearing, topical corticosteroids and antibiotic abuse. Nowadays, topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities. However, the pathogenesis of FK, especially the immunologic mechanism within it, has not yet been deeply clarified. A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis. Meanwhile, the immune protection strategies are also urgently required to manage FK. This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK, in hope of providing valuable reference information for more effective anti-fungal treatment.

The Asian seabass, Lates calcarifer , is a key species in Asian aquaculture due to its nutritional value and adaptability. However, disease outbreaks, particularly viral and bacterial infections, pose significant challenges to its production. Immunostimulants offer promising solutions but raise safety concerns. Paraprobiotics and postbiotics (CPP) emerge as safer alternatives, exerting health benefits without live microorganisms. This study investigated the potential of probiotic paraprobiotic and postbiotic supplements derived from Bacillus subtilis to enhance the immune response and antioxidant capacity of Asian seabass and improve their resistance to Streptococcus iniae infection. Analysis of antioxidant activity and lipid peroxidation revealed significant improvements in fish supplemented with CPP, indicating their effectiveness in mitigating oxidative stress. Immunological assays demonstrated enhanced growth performance and serum immunity, including increased alternative complement activity, immunoglobulin levels, and phagocytic activity, in supplemented fish. Furthermore, upregulated expression of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and pattern recognition receptors (NLRC3, TLR22, MDA5) in immune tissues. Fish supplemented with CPP exhibited higher resistance and survival rates against S. iniae infection challenge compared to control groups. The study elucidates the mechanisms underlying the immunomodulatory effects of CPP, shedding light on their potential applications in aquaculture. • Paraprobiotics and postbiotics (CPP) enhance fish immunity by modulating pattern recognition receptor (PPRs). • Feeding Asian seabass with CCP supplements improved growth and immune responses. • CPP improve fish health by modulating antioxidant systems. • CCP could enhance fish resistance and survival rates against S. iniae infection. [ABSTRACT FROM AUTHOR]

Persistent infections of the skin with the human papillomavirus of genus beta (β-HPV) in immunocompetent individuals are asymptomatic, but in immunosuppressed patients, β-HPV infections exhibit much higher viral loads on the skin and are associated with an increased risk of skin cancer. Unlike with HPV16, a high-risk α-HPV, the impact of β-HPV early genes on the innate immune sensing of viral nucleic acids has not been studied. Here, we used primary skin keratinocytes and U2OS cells expressing HPV8 or distinct HPV8 early genes and well-defined ligands of the nucleic-acid-sensing receptors RIG-I, MDA5, TLR3, and STING to analyze a potential functional interaction. We found that primary skin keratinocytes and U2OS cells expressed RIG-I, MDA5, TLR3, and STING, but not TLR7, TLR8, or TLR9. While HPV16-E6 downregulated the expression of RIG-I, MDA5, TLR3, and STING and, in conjunction with HPV16-E7, effectively suppressed type I IFN in response to MDA5 activation, the presence of HPV8 early genes showed little effect on the expression of these immune receptors, except for HPV8-E2, which was associated with an elevated expression of TLR3. Nevertheless, whole HPV8 genome expression, as well as the selective expression of HPV8-E1 or HPV8-E2, was found to suppress MDA5-induced type I IFN and the proinflammatory cytokine IL-6. Furthermore, RNA isolated from HPV8-E2 expressing primary human keratinocytes, but not control cells, stimulated a type I IFN response in peripheral blood mononuclear cells, indicating that the expression of HPV8-E2 in keratinocytes leads to the formation of stimulatory RNA ligands that require the active suppression of immune recognition. These results identify HPV8-E1 and HPV8-E2 as viral proteins that are responsible for the immune escape of β-HPV from the innate recognition of viral nucleic acids, a mechanism that may be necessary for establishing persistent β-HPV infections. [ABSTRACT FROM AUTHOR]

• The contribution of neuronal TLRs to CNS pathologies has been underappreciated. • Neuronal TLRs play context-dependent roles in neurodegenerative diseases and CNS injuries. • TLRs in primary sensory neurons mediate neuropathic pain. • Neuronal TLRs modulate dendrite and axon outgrowth and cell viability. • Neuronal TLRs utilize both canonical and non-canonical signaling pathways. Toll-like receptors (TLRs) are innate immune receptors that are expressed in immune cells as well as glia and neurons of the central and peripheral nervous systems. They are best known for their role in the host defense in response to pathogens and for the induction of inflammation in infectious and non-infectious diseases. In the central nervous system (CNS), TLRs modulate glial and neuronal functions as well as innate immunity and neuroinflammation under physiological or pathophysiological conditions. The majority of the studies on TLRs in CNS pathologies investigated their overall contribution without focusing on a particular cell type, or they analyzed TLRs in glia and infiltrating immune cells in the context of neuroinflammation and cellular activation. The role of neuronal TLRs in CNS diseases and injuries has received little attention and remains underappreciated. The primary goal of this review is to summarize findings demonstrating the pivotal and unique roles of neuronal TLRs in neuropathic pain, Alzheimer's disease, Parkinson's disease and CNS injuries. We discuss how the current findings warrant future investigations to better define the specific contributions of neuronal TLRs to these pathologies. We underline the paucity of information regarding the role of neuronal TLRs in other neurodegenerative, demyelinating, and psychiatric diseases. We draw attention to the importance of broadening research on neuronal TLRs in view of emerging evidence demonstrating their distinctive functional properties. [ABSTRACT FROM AUTHOR]

Intracellular pathogens pose a significant threat to animals. In defense, innate immune sensors attempt to detect these pathogens using pattern recognition receptors that either directly detect microbial molecules or indirectly detect their pathogenic activity. These sensors trigger different forms of regulated cell death, including pyroptosis, apoptosis, and necroptosis, which eliminate the infected host cell niche while simultaneously promoting beneficial immune responses. These defenses force intracellular pathogens to evolve strategies to minimize or completely evade the sensors. In this review, we discuss recent advances in our understanding of the cytosolic pattern recognition receptors that drive cell death, including NLRP1, NLRP3, NLRP6, NLRP9, NLRC4, AIM2, IFI16, and ZBP1. [ABSTRACT FROM AUTHOR]

Pattern recognition receptors Mincle and NOD2 have been implicated in mycobacterial immunity. However, knockout (KO) animal infection studies with Mycobacterium tuberculosis (Mtb) have had mild/delayed phenotypes. Given that genetic susceptibility to infectious diseases can be polygenic, we hypothesized that murine double knockout (DKO) of Mincle and Nod2 would result in exacerbation of altered immunity to mycobacterial infection leading to a more extreme phenotype than either KO alone. To test this hypothesis, we monitored bacterial burden, immune responses and survival following in vivo infections with Mtb in DKO mice for comparison to wildtype (WT) and single KOs. Bacterial burden and immune responses were not significantly affected at 3 and 6 weeks after infection in all mutant mice. At later timepoints, Nod2 -KO mice had reduced survival compared to wildtype mice, and Mincle -KO survival was intermediate. Unexpectedly, dual disruption had no further effect; rather, DKO mice phenocopied Nod2 -KO mice. We observed that Mtb -related death, exclusively in mice with disrupted Nod2 , was accompanied by greater pulmonary cell death and distinct large necrotic foci. Therefore, determining how these receptors contribute to mycobacterial resistance will require analysis of immunophenotypes and their consequences on host pathology. [ABSTRACT FROM AUTHOR]

Inflammasomes are important multiprotein regulatory complexes of innate immunity and have recently emerged as playing divergent roles in numerous inflammation-associated cancers. Among these include gastric cancer (GC), the third leading cause of cancer-associated death worldwide, and we have previously discovered a pro-tumorigenic role for the key inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) in the spontaneous genetic gp130 F/F mouse model for GC. However, the identity of the specific pattern recognition receptors (PRRs) that activate tumor-promoting inflammasomes during GC is unknown. Here, we investigated the role of the best-characterized inflammasome-associated PRR, nucleotide-binding domain, and leucine-rich repeat containing receptor, pyrin domain-containing (NLRP) 3, in GC. In gastric tumors of gp130 F/F mice, although NLRP3 expression was elevated at the mRNA (qPCR) and protein (immunohistochemistry) levels, genetic ablation of NLRP3 in gp130 F/F: Nlrp3 -/- mice did not alleviate the development of gastric tumors. Similarly, cellular processes associated with tumorigenesis in the gastric mucosa, namely, proliferation, apoptosis, and inflammation, were comparable between gp130 F/F and gp130 F/F: Nlrp3 -/- mice. Furthermore, inflammasome activation levels, determined by immunoblotting and immunohistochemistry for cleaved Caspase-1, which along with ASC is another integral component of inflammasome complexes, were unchanged in gp130 F/F and gp130 F/F: Nlrp3 -/- gastric tumors. We also observed variable NLRP3 expression levels (mRNA and protein) among independent GC patient cohorts, and NLRP3 was not prognostic for survival outcomes. Taken together, these data suggest that NLRP3 does not play a major role in promoting inflammasome-driven gastric tumorigenesis, and thus pave the way for further investigations to uncover the key inflammasome-associated PRR implicated in GC. [ABSTRACT FROM AUTHOR]

Insects occupy a central position in the biosphere. They are able to resist infections even though they lack an adaptive immune system. Drosophila melanogaster has been used as a potent genetic model to understand innate immunity both in invertebrates and vertebrates. Its immune system includes both humoral and cellular arms. Here, we review how the distinct immune responses are triggered upon sensing infections, with an emphasis on the mechanisms that lead to systemic humoral immune responses. As in plants, the components of the cell wall of microorganisms are detected by dedicated receptors. There is also an induction of the systemic immune response upon sensing the proteolytic activities of microbial virulence factors. The antiviral response mostly relies on sensing double-stranded RNAs generated during the viral infection cycle. This event subsequently triggers either the viral short interfering RNA pathway or a cGAS-like/STING/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Inflammasomes are important multiprotein regulatory complexes of innate immunity and have recently emerged as playing divergent roles in numerous inflammation-associated cancers. Among these include gastric cancer (GC), the third leading cause of cancer-associated death worldwide, and we have previously discovered a pro-tumorigenic role for the key inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) in the spontaneous genetic gp130F/F mouse model for GC. However, the identity of the specific pattern recognition receptors (PRRs) that activate tumor-promoting inflammasomes during GC is unknown. Here, we investigated the role of the best-characterized inflammasome-associated PRR, nucleotide-binding domain, and leucine-rich repeat containing receptor, pyrin domain-containing (NLRP) 3, in GC. In gastric tumors of gp130F/F mice, although NLRP3 expression was elevated at the mRNA (qPCR) and protein (immunohistochemistry) levels, genetic ablation of NLRP3 in gp130F/F:Nlrp3-/- mice did not alleviate the development of gastric tumors. Similarly, cellular processes associated with tumorigenesis in the gastric mucosa, namely, proliferation, apoptosis, and inflammation, were comparable between gp130F/F and gp130F/F:Nlrp3-/- mice. Furthermore, inflammasome activation levels, determined by immunoblotting and immunohistochemistry for cleaved Caspase-1, which along with ASC is another integral component of inflammasome complexes, were unchanged in gp130F/F and gp130F/F:Nlrp3-/- gastric tumors. We also observed variable NLRP3 expression levels (mRNA and protein) among independent GC patient cohorts, and NLRP3 was not prognostic for survival outcomes. Taken together, these data suggest that NLRP3 does not play a major role in promoting inflammasome-driven gastric tumorigenesis, and thus pave the way for further investigations to uncover the key inflammasome-associated PRR implicated in GC.

Pattern recognition receptors Mincle and NOD2 have been implicated in mycobacterial immunity. However, knockout (KO) animal infection studies with Mycobacterium tuberculosis (Mtb) have had mild/delayed phenotypes. Given that genetic susceptibility to infectious diseases can be polygenic, we hypothesized that murine double knockout (DKO) of Mincle and Nod2 would result in exacerbation of altered immunity to mycobacterial infection leading to a more extreme phenotype than either KO alone. To test this hypothesis, we monitored bacterial burden, immune responses and survival following in vivo infections with Mtb in DKO mice for comparison to wildtype (WT) and single KOs. Bacterial burden and immune responses were not significantly affected at 3 and 6 weeks after infection in all mutant mice. At later timepoints, Nod2-KO mice had reduced survival compared to wildtype mice, and Mincle-KO survival was intermediate. Unexpectedly, dual disruption had no further effect; rather, DKO mice phenocopied Nod2-KO mice. We observed that Mtb-related death, exclusively in mice with disrupted Nod2, was accompanied by greater pulmonary cell death and distinct large necrotic foci. Therefore, determining how these receptors contribute to mycobacterial resistance will require analysis of immunophenotypes and their consequences on host pathology.

The ability to distinguish pathogens from self-antigens is one of the most important functions of the immune system. However, this simple self versus non-self assignment belies the complexity of the immune response to threats. Immune responses vary widely and appropriately according to a spectrum of threats and only recently have the mechanisms for controlling this highly textured process emerged. A primary mechanism by which this controlled decision-making process is achieved is via Toll-like receptor (TLR) signaling and the subsequent activation of the immune response coincident with the presence of pathogenic organisms or antigens, including lipid mediators. While immune activation is important, the appropriate regulation of such responses is also critical. Recent findings indicate a parallel pathway by which responses to both viral and bacterial infections is controlled via the secretion of soluble TLR2 (sTLR2). sTLR2 is able to bind a wide range of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). sTLR2 has been detected in many bodily fluids and is thus ubiquitous in sites of pathogen appearance. Interestingly, growing evidence suggests that sTLR2 functions to sequester PAMPs and DAMPs to avoid immune activation via detection of cellular-expressed TLRs. This immune regulatory function would serve to reduce the expression of the molecules required for cellular entry, and the recruitment of target cells following infection with bacteria and viruses. This review provides an overview of sTLR2 and the research regarding the mechanisms of its immune regulatory properties. Furthermore, the role of this molecule in regulating immune activation in the context of HIV infection via sTLR2 in breast milk provides actionable insights into therapeutic targets across a variety of infectious and inflammatory states.

Peptidoglycan Recognition Proteins (PGRPs) are a diverse group of proteins involved in innate immunity. In particular, PGRPs have been shown to participate in immune pattern recognition in various mollusks. However, they have not been described in Caenogastropoda, a large molluscan group comprising sea, freshwater and land snails. In this study, four short PGRPs with molecular weights ranging from 21 to 34 kDa and their isoforms were identified and structurally characterized in the kidney and hemocytic transcriptomes of a caenogastropod mollusk Littorina littorea. All of them (Ll PGRP1-4) are secretory, possess a signal peptide and a characteristic N-terminal N -acetylmuramoyl- l -alanine amidase (Ami) domain with conserved Zn2+ binding- and amidase catalytic sites. The shortest proteins, Ll PGRP1 and Ll PGRP2, have no additional conserved motifs on the N-terminus. In longer and most abundantly expressed Ll PGRP3 and Ll PGRP4 the Ami-domain is combined with an N-terminal SH3-domain and a cysteine-rich motif, respectively. Expression analysis showed that Ll PGRPs of the common periwinkle were uninvolved in the immune response to infection with trematode Himasthla elongata though they might act in antibacterial defense. • Four short PGRPs (Ll PGRPs) were identified and structurally characterized in L. littorea. • All of them are secretory, possess a characteristic Ami domain with conserved amidase catalytic sites. • In two of them Ami-domain is combined with an N-terminal SH3-domain or a cysteine-rich motif. • Ll PGRPs were uninvolved in the immune response to infection with trematode Himasthla elongata. [ABSTRACT FROM AUTHOR]

Summary: Innate immunity plays a major role in controlling viral infections. Recent exploration of sodium taurocholate co‐transporting polypeptide receptor as specific hepatitis B virus (HBV) receptor in human hepatocytes has provided appropriate cell culture tools to study the innate immunity of hepatocytes and its cross talk with HBV. In this review, we give a brief update on interaction between HBV and innate immunity using the currently available in vitro cellular models that support the complete life cycle of HBV. We will discuss how HBV can act as a 'stealth' virus to counteract the innate immune responses mediated by the pathogen recognition receptors of hepatocytes and escape the first line of surveillance of the host immune system. We give an overview of the cellular components of innate immunity that present in these in vitro models and discuss how activating these innate immunity components may contribute to the eradication of HBV infection. [ABSTRACT FROM AUTHOR]

Induction of the antiviral innate immune response is highly regulated at the RNA level, particularly by RNA modifications. Recent discoveries have revealed how RNA modifications play key roles in cellular surveillance of nucleic acids and in controlling gene expression in response to viral infection. These modifications have emerged as being essential for a functional antiviral response and maintaining cellular homeostasis. In this review, we will highlight these and other discoveries that describe how the antiviral response is controlled by modifications to both viral and cellular RNA, focusing on how mRNA cap modifications, N6‐methyladenosine, and RNA editing all contribute to coordinating an efficient response that properly controls viral infection. [ABSTRACT FROM AUTHOR]

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Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics.

C-type lectins (CTLs) are glycan-binding pattern recognition receptors (PRRs) that can bind to carbohydrates on pathogen surfaces, triggering immune responses in shrimp innate immunity. In this study, a unique Ca2+-inhibited CTL named Fc Lec was identified and characterized in Chinese shrimp Fenneropenaeus chinensis. The full-length cDNA sequence of Fc Lec was 976 bp (GenBank accession number KU361826), with a 615 bp open reading frame (ORF) encoding 204 amino acids. Fc Lec possesses a C-type lectin-like domain (CTLD) containing four conserved cysteines (Cys105, Cys174, Cys192, and Cys200) and two sugar-binding site structures (QPD and LNP). The tertiary structure of Fc Lec deduced revealed three α-helices and eight β-pleated sheets. The mRNA expression levels of Fc Lec in hemocytes and the hepatopancreas were markedly elevated after stimulation with Vibrio anguillarum and white spot syndrome virus (WSSV). The recombinant Fc Lec protein exhibited Ca2+-independent hemagglutination and bacterial agglutination, but these activities were observed only in the presence of EDTA to chelate metal ions. These findings suggest that Fc Lec plays important and functionally distinct roles in the shrimp's innate immune response to bacteria and viruses, enriching the current understanding of the relationship between CTL activity and Ca2+ in invertebrates. [Display omitted] • A novel CTL, Fc Lec, were identified from F. chinensis. • Fc Lec plays distinct and significant roles in the innate immune system's reaction to microbial assaults. • Fc Lec exhibits Ca2+-independent and even Ca2+-inhibited activity. [ABSTRACT FROM AUTHOR]

Subclinical endometritis (SE) is one cause of repeat breeder syndrome (RBS). When endometrial cells come into contact with antigens during inflammatory events like endometritis, they act like innate immune system cells. Ovsynch-based therapies stimulate the innate immune system, which is how they may be able to cure SE and then RBS. This study aimed to assess the effects of presynch-10 and ovsynch applications on mRNA expressions of some endometrial Toll- and Nod-like receptors (TLRs and NLRs) in cows with RBS. A total of 40 repeat breeder cows were used in the study. The presynch-10 and ovsynch protocols were used in group 1 (G1, n=20), and no protocol was used in group 2 (G2, n=20). Endometrial samples were collected before and after the synchronization protocols in G1. In G2, samples were collected, and after waiting time up to the duration of synchronization protocol in G1, samples were taken again. The expression profiles of the genes being investigated were examined using RT-qPCR. NLRC4, NALP3 and TLR4 were basically expressed in all of the samples while NOD2 expression was completely undetectable. There was a statistical difference when NOD1 and TLR2 expressions in the second samples were compared between G1 and G2 (P

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive symmetric inflammation of the joints resulting in bone erosion and cartilage destruction with a progressive loss of function and joint deformity. An increased number of findings support the role of innate immunity in RA: many innate immune mechanisms are responsible for producing several cytokines and chemokines involved in RA pathogenesis, such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6, and IL-1. Pattern recognition receptors (PRRs) play a crucial role in modulating the activity of the innate arm of the immune response. We focused our attention over the years on the expression and functions of a specific class of PRR, namely formyl peptide receptors (FPRs), which exert a key function in both sustaining and resolving the inflammatory response, depending on the context and/or the agonist. We performed a broad review of the data available in the literature on the role of FPRs and their ligands in RA. Furthermore, we queried a publicly available database collecting data from 90 RA patients with different clinic features to evaluate the possible association between FPRs and clinic-pathologic parameters of RA patients.

Pattern recognition receptors (PRRs) are evolutionarily ancient and crucial components of innate immunity, recognizing danger-associated molecular patterns (DAMPs) and activating host defenses. Basal non-bilaterian animals such as cnidarians must rely solely on innate immunity to defend themselves from pathogens. By investigating cnidarian PRR repertoires we can gain insight into the evolution of innate immunity in these basal animals. Here we utilize the increasing amount of available genomic resources within Cnidaria to survey the PRR repertoires and downstream immune pathway completeness within 15 cnidarian species spanning two major cnidarian clades, Anthozoa and Medusozoa. Overall, we find that anthozoans possess prototypical PRRs, while medusozoans appear to lack these immune proteins. Additionally, anthozoans consistently had higher numbers of PRRs across all four classes relative to medusozoans, a trend largely driven by expansions in NOD-like receptors and C-type lectins. Symbiotic, sessile, and colonial cnidarians also have expanded PRR repertoires relative to their non-symbiotic, mobile, and solitary counterparts. Interestingly, cnidarians seem to lack key components of mammalian innate immune pathways, though similar to PRR numbers, anthozoans possess more complete immune pathways than medusozoans. Together, our data indicate that anthozoans have greater immune specificity than medusozoans, which we hypothesize to be due to life history traits common within Anthozoa. Overall, this investigation reveals important insights into the evolution of innate immune proteins within these basal animals.