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Gender medicine is now an approach that can no longer be neglected and must be considered in scientific research. We investigated the systemic and mucosal immune response in a population of women living with HIV (WLWH) who were receiving successful ART and the sexual and psychological repercussions of HIV infection on the women’s health. As control group, healthy women (HW) matched for age and sex distribution, without any therapy, were included. In summary, our study highlighted the persistence of immune-inflammatory activation in our population, despite virological suppression and a normal CD4 cell count. We found a hyperactivation of the systemic monocyte and an increase in inflammatory cytokine concentrations at the systemic level. The analysis carried out showed a significantly higher risk of HPV coinfection in WLWH compared to HW. Furthermore, our data revealed that WLWH have a profile compatible with sexual dysfunction and generalized anxiety disorders. Our study underlines that patients living with HIV should be evaluated by multidisciplinary teams. These findings also support the idea that more and different immunological markers, in addition to those already used in clinical practice, are needed. Further studies should be carried out to clarify which of these could represent future therapy targets.

Background Canine distemper virus (CDV) infection of ferrets, dogs, and giant pandas causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system. In this study, we tested a new candidate CDV vaccine-CDV nanoparticles-based on hemagglutinin protein. Methods The nanoparticles were generated from conformation-stabilized CDV hemagglutinin tetramers. Immune responses against CDV were evaluated in mice. Immunization was initiated 6 weeks after birth and boosted two times with 4-week intervals. The blood and mucosal samples were collected 2 weeks after each immunization. Results Vaccination with CDV nanoparticles elicited high levels of IgG antibody titers in mice (approximately sevenfold to eightfold higher than that obtained with soluble CDV H protein) and mucosal immune responses and developed increased CDV-specific neutralizing antibody. The mice that received nanoparticles showed significantly higher IFN-γ- and IL-4-secreting cell population in the spleen and lymph node compared with mice immunized with soluble H protein. The co-stimulatory molecular expression of CD80 and CD86 on the surface of DCs was also upregulated. Conclusion The results demonstrate that self-assembly into nanoparticles can increase the immunogenicity of vaccine antigens, and nanoparticles assembled from conformation-stabilized CDV H protein can serve as a new CDV vaccine.

Recent advancements in the field of in vitro transcribed mRNA (IVT-mRNA) vaccination have attracted considerable attention to such vaccination as a cutting-edge technique against infectious diseases including COVID-19 caused by SARS-CoV-2. While numerous pathogens infect the host through the respiratory mucosa, conventional parenterally administered vaccines are unable to induce protective immunity at mucosal surfaces. Mucosal immunization enables the induction of both mucosal and systemic immunity, efficiently removing pathogens from the mucosa before an infection occurs. Although respiratory mucosal vaccination is highly appealing, successful nasal or pulmonary delivery of nucleic acid-based vaccines is challenging because of several physical and biological barriers at the airway mucosal site, such as a variety of protective enzymes and mucociliary clearance, which remove exogenously inhaled substances. Hence, advanced nanotechnologies enabling delivery of DNA and IVT-mRNA to the nasal and pulmonary mucosa are urgently needed. Ideal nanocarriers for nucleic acid vaccines should be able to efficiently load and protect genetic payloads, overcome physical and biological barriers at the airway mucosal site, facilitate transfection in targeted epithelial or antigen-presenting cells, and incorporate adjuvants. In this review, we discuss recent developments in nucleic acid delivery systems that target airway mucosa for vaccination purposes.

Objective: Children with no pathogenic bacteria in the nasopharynx are unlikely to have acute bacterial sinusitis. We evaluated whether information on clinical presentation, viral co-detection, and mucosal cytokine levels could be used to predict presence of bacteria in the nasopharynx.Method: We obtained nasopharyngeal (NP) swabs from children diagnosed with acute sinusitis. NP swabs were processed for bacterial culture, viral PCR testing, and cytokine expression. We examined whether results of the bacterial culture could be predicted based on the presence of clinical information, presence of viruses or mucosal cytokine levels.Results: We enrolled 174 children; 123 (71%) had a positive culture for potentially pathogenic bacteria and 51 (29%) had normal flora. 122/174 (70%) tested positive for one or more viruses. Compared to children with normal flora, children with pathogenic bacteria were more likely to have viruses (p < 0.01), but this relationship disappeared when we adjusted for age. Children with pathogenic bacteria in their nasopharynx and children with normal flora had similar levels of nasal cytokines.Conclusion: In children with clinically diagnosed acute sinusitis, clinical presentation, levels of nasal cytokines, and presence of viruses do not differentiate children with and without pathogenic bacteria in their nasopharynx.

Infections have been considered to play a critical role in the pathogenesis of IgA nephropathy (IgAN) because synpharyngitic hematuria is a common feature in IgAN. However, how infections participate in this process is still debated. More recent studies have also revealed that the alteration of the gut microbiome exerts a profound effect on host immune responses, contributing to the etiology or progression of autoimmunity. Considering IgA as the first line of defense against bacterial and viral antigens, this review evaluates the relationships among intestinal infections, gut microbiome, and IgA for a better understanding of the pathogenesis of IgAN. Moreover, as a prototype of IgA immunity, we provide detailed clarification of IgAN pathogenesis to shed light on other diseases in which IgA plays a role. Finally, we discuss potential therapies focusing on microbes and mucosal immune responses in IgAN.

Background Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. Objectives To evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. Methods Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including SARS-CoV-2 polymerase chain reaction (PCR)+ patients (n = 64) as well as PCR+ and PCR– healthcare workers (n = 109). Results SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases were often transiently positive, whereas serum IgG titers remained negative or became positive 12–14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some healthcare workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids inversely correlated with age. Conclusions Systemic antibody production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA titers seen in patients with severe ARDS, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion., Graphical abstract, Our study suggests a model where the extent and duration of SARS-CoV-2-related clinical symptoms correlates with the systemic and mucosal virus-specific humoral immune responses, with implications for seroprevalence studies.

Probiotic bacteria, including the Enterococcus faecium strain, can improve intestinal mucosal health by several mechanisms, including modulation of the immune response, as well as by improving the protective function of the epithelial barrier. In this study, we tested the effect of Enterococcus faecium AL41 on the acute phase proteins response (blood), gene expression of selected molecules of mucosal immunity (immunoglobulin A, mucin-2, insulin-like growth factor 2) and mucus production (all parts of the small intestine) in broilers. Eighty broiler chicks were divided into two groups: a control and E. faecium AL41 (birds were inoculated with AL41 for 7 days) group. The whole experiment lasted 11 days. Our results revealed that the administration of E. faecium AL41 had no substantial effect on the concentrations of acute phase proteins, but we recorded a significant increase in β- and γ-globulin fractions at the end of the experiment, which may indicate an improvement in the immune status. A significant prolonged stimulatory effect of E. faecium AL41 on the relative expression of molecules (immunoglobulin A, mucin-2) as well as on the dynamic of mucus production in the chicken intestine was observed. In addition, AL41 significantly reduced the total number of enterococci in the cecum and faeces.

β-conglycinin from soybean has been recognized as one of the major feed allergens. This study investigated the effects of β-conglycinin-induced allergic sensitization on chicks’ small intestines. A total of 40 7-day-old (100 g) chicks were divided into four groups as control, β-conglycinin 1 h, β-conglycinin 6 h, and β-conglycinin 12 h. All treatment groups were administered 60 mg of β-conglycinin/chick and small intestine samples were collected. β-conglycinin-induced allergic sensitization marginally damages the epithelium lining of the duodenum villi and, in addition, significantly increases the accumulation of mast cells in the lamina propria and crypt of the duodenum. Moreover, the TNF-α level significantly increased in all β-conglycinin groups. IL-8 and IL-2 were significantly downregulated in the 1 h group; however, there were increases for the 6 h and 12 h groups. These results suggest that β-conglycinin may lead to an inflammatory response in the chicks’ small intestines.

Anoplocephala perfoliata is the commonest equine tapeworm, the adult parasites are attached in groups close to the ileocaecal valve causing marked inflammatory pathology. This work aimed to characterize the nature of the in vivo mucosal immune response to A perfoliata, and to investigate the role of A perfoliata excretory-secretory components in modulating in vitro immune responses. Real-time PCR detected elevation of IL13 and TGFβ transcription in early-stage A perfoliata infection. In late-stage infection, IL-13, IL4 and Ifn transcripts were reduced while the regulatory cytokines, TGFβ, IL10 and the transcription factor FOXP3 were increased in tissue close to the site of A perfoliata attachment; indicating downregulation of T-cell responses to A perfoliata. In vitro, A perfoliata excretory-secretory products induced apoptosis of the Jurkat T-cell line and premature cell death of ConA stimulated equine peripheral blood leucocytes. Analysis of cytokine transcription patterns in the leucocyte cultures showed a marked inhibition of IL-1 and IL-2 suggesting that a lack of T-cell growth factor transcription underlies the mechanism of the induced equine T-cell death. These preliminary findings suggest A perfoliata may have the ability to down-regulate host T-cell responses.

Background Polyamines are essential for cell growth and beneficial for intestinal maturation. To evaluate the effects of putrescine on alleviating intestinal atrophy and underlying molecular mechanisms, both in vivo feeding trial and in vitro cell culture were conducted. Weanling pigs were fed a diet supplemented with 0, 0.1%, 0.2% or 0.3% putrescine dihydrochloride, whereas porcine intestinal epithelial cells (IPEC-J2) were challenged with lipopolysaccharide (LPS) in the presence of 200 μmol/L putrescine. Results Dietary supplementation with 0.2% putrescine dihydrochloride decreased the incidence of diarrhea with an improvement in intestinal integrity. Inhibition of ornithine decarboxylase activity decreased the proliferation and migration of IPEC-J2 cells, and this effect was alleviated by the supplementation with putrescine. The phosphorylation of extracellular signal regulated kinase and focal adhesion kinase was enhanced by putrescine. LPS increased the expression of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-8], and inhibited cell proliferation and migration in IPEC-J2 cells. Adding exogenous putrescine suppressed the expression of TNF-α, IL-6 and IL-8, and recovered cell migration and proliferation in LPS-treated IPEC-J2 cells. Dietary putrescine supplementation also reduced the mRNA levels of TNF-α, IL-6 and IL-8 and their upstream regulator nuclear receptor kappa B p65 subunit in the jejunal mucosa of piglets. Conclusions Dietary supplementation with putrescine mitigated mucosal atrophy in weanling piglets through improving anti-inflammatory function and suppressing inflammatory response. Our results have important implications for nutritional management of intestinal integrity and health in weanling piglets and other neonates.

This study determined the effects of chicken egg yolk antibodies (IgY) on immune responses in the intestinal mucosal of mice infected with Salmonella typhimurium. Sixty, 28-day-old mice were divided into 4 groups and treated with streptomycin or sterile water for 2 days followed by 1 day without treatment. The control group was unchallenged whereas the mice in the other three groups were treated twice with 109 CFU mL− 1S. typhimurium. For the next 3 days, control mice continued to receive no treatment whereas the mice in the remaining three groups were orally administered with 20 mg mL− 1 of specific IgY, 20 mg mL− 1 of nonspecific IgY or PBS. S. typhimurium activated gut-associated lymphoid tissue, increasing the release of IFN-γ and TNF-α in the mucosa and increased the number of activated T-lymphocytes and cytotoxic T-γδ. Specific IgY attenuated the increase in IFN-γ and TNF-α and the decrease in IL-10. S. typhimurium induced mobilization of CD8+ and CD8+ TCRγδ T cells in the epithelium and CD4+ and CD8+ T cells in the lamina propria reflecting an inflammatory process that was attenuated by IgY. These results suggest that specific IgY modulates intestinal mucosal immune responses during a S. typhimurium infection., Highlights • Specific IgY could effectively alleviate S. typhimurium-inflicted damage to the jejunum. • Specific IgY attenuated an increase in the cytokines IFN-γ and TNF-α in the mucosa. • IgY attenuated changes in lymphocyte numbers in Peyer's patches, epithelium and lamina propria. • Specific IgY has an important immune-modulatory role on the intestinal mucosal immune response. • Specific IgY limits the consequences of intestinal inflammation induced by S. typhimurium.

Background: Host factors play an important role in pathogenesis and disease outcome in Clostridium difficile infection (CDI), and characterization of these responses could uncover potential host biomarkers to complement existing microbe-based diagnostics. Methods: We extracted RNA from fecal samples of patients with CDI and profiled human mRNA using amplicon-based next-generation sequencing (NGS). We compared the fecal host mRNA transcript expression profiles of patients with CDI to controls with non-CDI diarrhea. Results: We found that the ratio of human actin gamma 1 (ACTG1) to 16S ribosomal RNA (rRNA) was highly correlated with NGS quality as measured by percentage of reads on target. Patients with CDI could be differentiated from those with non-CDI diarrhea based on their fecal mRNA expression profiles using principal component analysis. Among the most differentially expressed genes were ones related to immune response (IL23A, IL34) and actin-cytoskeleton function (TNNT1, MYL4, SMTN, MYBPC3, all adjusted P-values < 1 × 10−3). Conclusions: In this proof-of-concept study, we used host fecal transcriptomics for non-invasive profiling of the mucosal immune response in CDI. We identified differentially expressed genes with biological plausibility based on animal and cell culture models. This demonstrates the potential of fecal transcriptomics to uncover host-based biomarkers for enteric infections.

Pneumonia is a major cause of death worldwide, with Streptococcus pneumoniae one of the most frequent pathogens [1, 2]. Control of the disease through vaccination has become an objective for preventive health care. The disease begins by the establishment of S. pneumoniae colonization in the upper respiratory tract (URT), followed by descent of the bacteria into the lower respiratory tract (LRT) to bring about a symptomatic infection [1, 2]. Nasopharyngeal carriage is clearly a prerequisite for all S. pneumoniae diseases [2], yet the immunological factors protecting against transition from carriage to disease are not adequately understood. Mucosal antibodies capable of preventing colonization may offer a key approach to protection [3–7]. Indeed, in animal models mucosal vaccines eliciting mucosal antibodies have proved to confer protection against local disease [5, 7, 8]. To develop better vaccination strategies, local immune mechanisms need to be explored in greater detail in humans. Pneumococcal vaccines, either as 23-valent polysaccharide preparations (PPV) or 10- or 13-valent polysaccharide vaccines conjugated to a protein carrier (PCV10 and PCV13, respectively), are licensed in many countries. PPV covers a broader spectrum of serotypes and confers protection against invasive pneumococcal disease, while the efficacy against local, noninvasive pneumonia remains controversial [9–11]. PCVs cover fewer serotypes and are not only effective against invasive pneumococcal disease [12], but also seem to confer some protection against noninvasive pneumonia (efficacy, 20%–37%) [13–15]. The insufficient ability of vaccines to elicit mucosal immune response has been suggested to account for their shortcomings in providing protection against local disease [5]. During an immune response, effector B lymphocytes (plasmablasts) do not spread equally across the body but instead are guided to travel to sites of expected antigen encounter. This tissue-specific homing of lymphocytes from blood into tissues is based on interaction between lymphocyte surface chemokine receptors (CCRs) and homing receptors with chemokines and specific homing receptor-ligands, addressins, on the endothelial cells of the target tissues, respectively [16, 17]. Tissue-specific homing receptors have been identified: L-selectin (CD62L) guides the lymphocytes to the peripheral lymph nodes [18], α4β7-integrin guides lymphocytes to the intestinal lamina propria [19], and cutaneous lymphocyte antigen (CLA) guides lymphocytes to skin tissue [20]. Analysis of the homing receptor and/or CCR profiles of the circulating plasmablasts provides an approach to evaluate the targeting of an immune response elicited at the site of antigen encounter [21–24]. The homing receptors guiding lymphocytes to the LRT have not been identified, but it has been suggested that instead of a single homing receptor, a variety of homing receptors are involved [16, 17, 25]. We have recently detected S. pneumoniae–specific plasmablasts in the circulation of humans with acute pneumococcal pneumonia [26]. These cells are presumed to originate in the LRT and to be responsible for distributing the immune response to various immunological compartments of the body [26]. Exploring these S. pneumoniae–specific plasmablasts allows study of the localization of the immune effector cells of the LRT. Comparing the homing receptor profiles of S. pneumoniae–specific plasmablasts between patients with pneumonia and volunteers who receive parenteral S. pneumoniae vaccines may throw new light on possible differences between natural infection and PPV or PCV in targeting the immune response.

Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. Our results demonstrate that oral administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α provided enhanced systemic and mucosal immune responses, as determined by serum hemagglutination inhibition antibody and NDV Ag-specific IgG as well as NDV Ag-specific IgA in lung and duodenal lavages of chickens immunized with inactivated ND vaccine via the intramuscular or intranasal route. Notably, combined oral administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α significantly enhanced systemic and mucosal immunity in ND-vaccinated chickens, compared to single administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α. In addition, oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α provided enhanced NDV Ag-specific proliferation of peripheral blood mononuclear cells and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results provide valuable insight into the modulation of systemic and mucosal immunity by incorporation of immunomodulatory chIL-18 and chIFN-α using Salmonella vaccines into existing ND vaccines.

Moraxella catarrhalis (Mcat) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied Mcat nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate Mcat proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of Mcat (30 vs. 22%, P = 0.0003) and Mcat-caused AOM rates (49 vs. 24%, P

Background The specific microclimate of alpine waterfalls with high levels of ionized water aerosols has been suggested to trigger beneficial immunological and psychological effects. In the present three-armed randomized controlled clinical study, we focused on effects on (i) immunological reagibility, on (ii) physiological stress responses, and on (iii) stress-related psychological parameters. Methods People with moderate to high stress levels (n = 65) spent an active sojourn with daily hiking tours in the National Park Hohe Tauern (Großkirchheim, Austria). Half of the group was exposed to water aerosol of an alpine waterfall for 1 h/day (first arm, n = 33), whereas the other half spent the same time at a distant site (second arm, n = 32). A third arm (control, n = 26) had no intervention (except vaccination) and stayed at home, maintaining their usual lifestyle. The effect of the interventions on the immune system was tested by oral vaccination with an approved cholera vaccine and measuring specific salivary IgA antibody titers. Lung function was determined by peak expiratory flow measurement. Electric skin conductance, heart rate, and adaption of respiration rate were assessed as physiological stress parameters. Psychological stress-related parameters were analyzed by questionnaires and scales. Results Compared to the control group, both intervention groups showed improvement of the lung function and of most physiological stress test parameters. Analysis of the mucosal immune response revealed a waterfall-specific beneficial effect with elevated IgA titers in the waterfall group. In line with these results, exposure to waterfall revealed an additional benefit concerning psychological parameters such as subjective stress perception (measured via visual analog scale), the Global Severity Index (GSI), and the Positive Symptom Total (PST). Conclusions Our study provides new data, which strongly support an “added value” of exposure to waterfall microclimate when combined with a therapeutic sojourn at high altitude including regular physical activity.

In normal individuals, the intestine is a site of intense immunological activity due to the continuous stimulation by luminal antigens mostly derived from the normal bacterial flora. This is reflected in the huge amount of IgA produced in the gut and the abundant T cells in the lamina propria and epithelium. It is also becoming clear that products of the normal flora may regulate the cytokine environment within the inductive sites of the mucosal immune responses, such as the Peyer's patches of the small bowel. Thus normal flora could either negatively or positively regulate specific immune responses by dictating the profile of locally released cytokines. For example, it is known that in Crohn's disease the antigens that drive the strongly polarized Th1 tissue-damaging response are derived from the normal bacteria flora. Emerging evidence also indicates that gut microflora can contribute to maintain the mucosal homeostasis by promoting the generation and/or expansion of counter-regulatory mechanisms.

Hemolytic uremic syndrome (HUS) is the major complication of gastrointestinal infections with enterohemorrhagic Escherichia coli (EHEC) and is mediated by the production of Shiga toxins (Stx). Although it has been previously reported that not only HUS patients but healthy children have anti-Stx antibodies, very little is known about how these infections impact on mucosal immune system to generate a specific immune response. This work aimed to evaluate the immune responses elicited after a single oral dose of EHEC in a mouse model of HUS at weaning. We found sequential activation of T and B lymphocytes together with an increased percentage of IgA-bearing B cells in Peyer´s patches and mesenteric lymph nodes. We also found fecal anti-EHEC IgA and serum anti-Stx2 IgG in EHEC-inoculated mice. Besides, these mice were partially protected against an intravenous challenge with Stx2. These data demonstrate that one episode of EHEC infection is enough to induce activation in the gut-associated lymphoid tissue, especially the B cell compartment, and lead to the production of specific IgA in mucosal tissue and the generation of systemic protection against Stx2 in a percentage of intragastrically inoculated mice. These data also support the epidemiologic observation that a second episode of HUS is very rare. Fil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Cabrera, Gabriel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Baschkier, Ariela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina Fil: Mejias, María Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Panek, Cecilia Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Miliwebsky, Elizabeth. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina Fil: Abrey Recalde, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Rivas, Marta. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina

7 páginas, 7 figuras, 2 tablas.-- et al., The aim of this study was to determine the effect of caloric restriction (CR) in mouse small intestine on the production and secretion of immunoglobulin (Ig) A, the population of lymphocytes in the lamina propria, and the expression of cytokines that mediate and regulate innate and adaptive immunity. One group of young Balb/c mice was fed ad libitum, while the CR group was fed ad libitum and fasted on alternate days. When mice were six months old, IgA levels in the proximal small intestine were quantified by enzyme-linked immunosorbent assay, while the number of IgA containing cells, CD4+ T cells and CD8+ T cells in the duodenal mucosa was determined by immunohistochemistry. Furthermore, the expression of several intestinal cytokines, the genes for α-chain IgA, and the polymeric Ig receptor (pIgR) were analyzed by real-time polymerase chain reaction. CR decreased the levels of IgA in the intestine, apparently a consequence of a reduced number of IgA+ cells in the lamina propria that decrease the production and secretion of this Ig, and a reduced secretion of S-IgA into the bile, which in turn discharges into the proximal intestine. Contrarily, CR increased the expression of genes for α-chain IgA, and the pIgR, indicating that transport of IgA was not a key factor in the decrease of this Ig. Additionally, CR modified the expression of genes for tumor necrosis factor-α, interferon-γ, tumor growth factor-β, interleukin (IL)-2 and IL-10, all of which regulate the synthesis of IgA and pIgR, the inflammatory response, and the immune response in the intestine., This work was supported by SIP-IPN and COFAA-IPN.

Background Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. Results In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220+ cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-Ad) were increased on CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. Conclusion These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.

Newcastle disease virus (NDV) is the causative agent of an economically important disease, which affects all species of birds worldwide. Current vaccination programs for NDV include the use of either low-virulent live-virus vaccines or inactivated vaccines to induce protective immunity while producing minimal adverse effects in birds. In order to further characterize the immune response elicited by live virus and inactivated NDV conventional vaccines in chickens, we evaluated the presence of specific antibodies in different secretions and in tissue culture supernatants of immunized birds. To this end, we analyzed all the samples by ELISA, using an indirect assay set up in the laboratory. Specific anti-NDV IgG antibodies were detected in tracheal and cloacal swabs and tracheal and intestinal washes of immunized animals. We also found specific anti-NDV IgG antibodies in tracheal and intestinal tissue culture supernatants, indicating that the IgG found in swabs and washes was not transudated from serum or, at least, was not all transudated from serum. Knowledge about the mechanisms involved in the immune response of chickens to different NDV vaccines should increase our understanding of the mucosal response against the virus and, eventually, provide new useful information for the development and evaluation of synthetic vaccines.

The health promoting effects ascribed to probiotic bacteria and fermented dairy products arise not only from bacteria themselves but also from metabolites derived from milk fermentation. Exopolysaccharides produced during milk fermentation and peptides derived from major milk proteins, when released during fermentation, are potential modulators of various regulatory processes in the body. The aim of this work was to increase the knowledge of the previously observed immunomodulating capacity of milk fermented by Lactobacillus helveticus R389 by the study of the mucosal immunomodulation exerted by the non-bacterial fraction of the milk fermented at a constant pH6 (NBFpH6). The effects on IL-6 production by small intestine epithelial cells, the profile of IgA+ and cytokine+ cells (IL-2, IL-6, IL-10, TNF-α and IFN-γ) induced in the gut lamina propria, and the levels of total and specific secretory IgA in the lumen of BALB/c mice that received NBFpH6 for 2, 5 or 7 days were examined. There was an increase in the number of IgA+, IL-10+, IL-2+ and IL-6+ cells after all feeding periods. Total S-IgA in the small intestine lumen increased in mice that received NBFpH6 for 2 days. However, no specific antibodies against NBFpH6 were detected. Feeding of NBFpH6 for 7 days significantly (P < 0.05) enhanced IL-6 secretion by small intestine epithelial cells. NBFpH6 induced a non-specific mucosal response that was down-regulated for protective immunity, enhancing IL-6 production by epithelial cells and IgA production in the small intestine. These events improve the immunological defenses at the intestinal level, increasing host protection against pathologies. Because mucosal immune responses induced by certain dietary antigens play a large part in the prevention of gastrointestinal diseases, the oral administration of a mucosal adjuvant such as NBFpH6 may positively affect the milieu of the intestinal lumen. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health condition of the host. Fil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Matar, Chantal. Université de Moncton. Département de Chimie et Biochimie; Canadá Fil: Palacios, Jorge Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina

Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmune disease. Both for food and clinical applications of lactobacilli, proper selection of wild type strains is crucial.For that purpose, eight different common Lactobacillus strains were analysed with respect to mucosal induction of pro- and anti-inflammatory cytokines, IgA-producing plasma cells in the gut, as well as systemic antibody responses against a parenterally administered antigen. Immunohistochemical analysis of cytokine-producing cells in the gut villi showed no significant induction of the cytokines IL-1α, IFN-γ, IL-4 or IL-10 after oral administration of wild type Lactobacillus strains. In contrast, oral administration of L. reuteri and L. brevis induced expression of the proinflammatory/Th1 cytokines TNF-α, IL-2 and/or IL-1β. Oral administration of these two strains and L. fermentum also significantly enhanced the IgG response against parenterally administered haptenated chicken gamma globulin (TNP-CGG). The five other strains did not show this adjuvanticity. L. reuteri induced relatively high levels of IgG2a compared to L. murines, a nonadjuving Lactobacillus strain.These findings imply that different Lactobacillus strains induce distinct mucosal cytokine profiles and possess differential intrinsic adjuvanticity. This suggests that rational Lactobacillus strain selection provides a strategy to influence cytokine expression and thereby influence immune responses. Copyright (C) 2000 Elsevier Science Ltd

Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmune disease. Both for food and clinical applications of lactobacilli, proper selection of wild type strains is crucial.For that purpose, eight different common Lactobacillus strains were analysed with respect to mucosal induction of pro- and anti-inflammatory cytokines, IgA-producing plasma cells in the gut, as well as systemic antibody responses against a parenterally administered antigen. Immunohistochemical analysis of cytokine-producing cells in the gut villi showed no significant induction of the cytokines IL-1α, IFN-γ, IL-4 or IL-10 after oral administration of wild type Lactobacillus strains. In contrast, oral administration of L. reuteri and L. brevis induced expression of the proinflammatory/Th1 cytokines TNF-α, IL-2 and/or IL-1β. Oral administration of these two strains and L. fermentum also significantly enhanced the IgG response against parenterally administered haptenated chicken gamma globulin (TNP-CGG). The five other strains did not show this adjuvanticity. L. reuteri induced relatively high levels of IgG2a compared to L. murines, a nonadjuving Lactobacillus strain.These findings imply that different Lactobacillus strains induce distinct mucosal cytokine profiles and possess differential intrinsic adjuvanticity. This suggests that rational Lactobacillus strain selection provides a strategy to influence cytokine expression and thereby influence immune responses. Copyright (C) 2000 Elsevier Science Ltd

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2,3,4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.