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Role of ABO secretor status in mucosal innate immunity and H. pylori infection.

ABSTRACT: The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens), which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation), which affect H. pylori adhesion targets and thus modulate host-bacterial interactions. Of particular relevance, gastric mucosal density of H. pylori, gastritis, and sialylation were all higher in secretor individuals compared to weak-secretors, the latter being apparently "protected." These results demonstrate that the secretor status plays an intrinsic role in resistance to H. pylori infection and suggest that the fucosylated secretor ABH antigens constitute interactive members of the human and primate mucosal innate immune system.

SUBMITTER: Linden S

PROVIDER: S-EPMC2174967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Lewis and ABO histo-blood types and the secretor status of patients hospitalized with COVID-19 implicate a role for ABO antibodies in susceptibility to infection with SARS-CoV-2.

Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets the respiratory and gastric epithelium, causing coronavirus disease 2019 (COVID-19). Tissue antigen expression variations influence host susceptibility to many infections. This study aimed to investigate the closely linked Lewis (FUT3) and ABO histo-blood types, including secretor (FUT2) status, to infections with SARS-CoV-2 and the corresponding severity of COVID-19.Study design and methodsPatients (Caucasians, n = 338) were genotyped for ABO, FUT3, and FUT2, and compared to a reference population of blood donors (n = 250,298). The association between blood types and severity of COVID-19 was addressed by dividing patients into four categories: hospitalized individuals in general wards, patients admitted to the intensive care unit with and without intubation, and deceased patients. Comorbidities were considered in subsequent analyses.ResultsPatients with blood type Lewis (a-b-) or O were significantly less likely to be hospitalized (odds ratio [OR] 0.669, confidence interval [CI] 0.446-0.971, OR 0.710, CI 0.556-0.900, respectively), while type AB was significantly more prevalent in the patient cohort (OR 1.519, CI 1.014-2.203). The proportions of secretors/nonsecretors, and Lewis a+ or Lewis b+ types were consistent between patients and controls. The analyzed blood groups were not associated with the clinical outcome as defined.DiscussionBlood types Lewis (a-b-) and O were found to be protective factors, whereas the group AB is suggested to be a risk factor for COVID-19. The antigens investigated may not be prognostic for disease severity, but a role for ABO isoagglutinins in SARS-CoV-2 infections is strongly suggested.

| S-EPMC8447157 | biostudies-literature

Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection.

Project description:Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1beta, IL-5, IL-12 p70, and MIP-1alpha was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF--kappaB pathway and has a negative feedback effect on NF-kappaB activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-kappaB activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization.

| S-EPMC2890768 | biostudies-literature

Effect of Donor and Recipient ABH-Secretor Status on ABO-Incompatible Living Donor Kidney Transplantation.

Project description:IntroductionABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation.MethodsData of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection.ResultsOf the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004).ConclusionsA weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.

| S-EPMC8236826 | biostudies-literature

Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.

Project description:Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2) is essential for transport of L-arginine (L-Arg) into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO) produced from inducible NO synthase (iNOS), or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2(-/-) mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2(-/-) mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2(-/-) mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.

| S-EPMC3237590 | biostudies-literature

Innate immunity - the hallmark of <i>Helicobacter pylori</i> infection in pediatric chronic gastritis.

Project description:BackgroundInnate immunity was found to be associated with both persistence of Helicobacter pylori (H. pylori) infection and increased risk of gastric cancer.AimTo identify the risk factors associated with H. pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children.MethodsWe performed a study of 155 children with digestive symptoms, who were divided into two groups according to the histopathological exam: Group 1 - 48 children with H. pylori-induced chronic gastritis, and Group 2 - control group.ResultsRural area and poor living conditions were significantly associated with H. pylori chronic gastritis (P = 0.0042/P < 0.0001). Both positive immunoglobulin A anti H. pylori and the rapid urease test were significantly associated with H. pylori infection (P < 0.0001). Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H. pylori chronic gastritis (P = 0.111/P = 0.284). We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils (P = 0.0225/P = 0.0292).ConclusionVariant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

| S-EPMC8362532 | biostudies-literature

Variant ABO blood group alleles, secretor status, and risk of pancreatic cancer: results from the pancreatic cancer cohort consortium.

Project description:Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk.We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression.An increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63).Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk.These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.

| S-EPMC3005538 | biostudies-literature

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Project description:Nucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are highly conserved cytosolic pattern recognition receptors that play, in combination with toll-like receptors, a critical role in innate immunity and inflammation. These proteins are characterized by a central oligomerization domain termed nucleotide-binding domain, and a protein interaction domain containing leucine-rich repeats. Some NLRs, including NOD1 and NOD2, sense the cytosolic presence of conserved bacterial molecular signatures and drive the activation of mitogen-activated protein kinase and the transcription factor NF-?B. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes known as inflammasomes. Activation of NLR proteins results in secretion of pro-inflammatory cytokines and subsequent inflammatory responses. The critical role of NLRs in innate immunity is underscored by the fact that polymorphisms within their genes are implicated in the development of several immune-mediated diseases, including inflammatory bowel disease. Over the past few years, the role of NLRs in intestinal homeostasis has been highlighted, however the mechanism by which dysfunction in these proteins leads to aberrant inflammation is still the focus of much investigation. The purpose of this review is to systematically evaluate the function of NLRs in mucosal innate immunity and understand how genetic or functional alterations in these components can lead to the disruption of intestinal homeostasis, and the subsequent development of chronic inflammation.

| S-EPMC4090755 | biostudies-literature

Association Between ABO Blood Groups and Helicobacter pylori Infection: A Meta-Analysis.

Project description:There is no consensus among the existing literature on the relationship between ABO blood groups and risk of Helicobacter pylori infection. However, histo-blood group carbohydrates are proposed to influence the risk of acquiring this pathogen via effects on adhesion to the gastric mucosa. The objective of this meta-analysis was to evaluate the association between ABO blood groups and H. pylori infection. All relevant epidemiological studies published in English (up to October 2017) was retrieved through an extensive systematic literature search of MEDLINE/PubMed databases. Pooled estimates of effects were obtained through the use of fixed and random effects meta-analyses. Individuals with O blood group were more likely to be infected with H. pylori (pooled odds ratio (OR) 1.163; 95% confidence interval (CI) 1.074-1.259; P?<?0.001). While individuals with B and AB blood group were less likely to be infected with H. pylori (OR 0.831; 95% CI 0.738-0.935; P?=?0.002 and OR 0.709; 95% CI 0.605-0.832; P?<?0.001, respectively). The results from this meta-analysis of observational studies suggest an estimated 16.3% increased odds of H. pylori infection amongst individuals with the O blood group. If this observed association is causal, a better understanding of the underlying mechanisms could provide indications to potential prevention strategies for H. pylori infection.

| S-EPMC6279815 | biostudies-other

The role of humoral innate immunity in hepatitis C virus infection.

Project description:Infection with Hepatitis C Virus (HCV) causes chronic disease in approximately 80% of cases, resulting in chronic inflammation and cirrhosis. Current treatments are not completely effective, and a vaccine has yet to be developed. Spontaneous resolution of infection is associated with effective host adaptive immunity to HCV, including production of both HCV-specific T cells and neutralizing antibodies. However, the supporting role of soluble innate factors in protection against HCV is less well understood. The innate immune system provides an immediate line of defense against infections, triggering inflammation and playing a critical role in activating adaptive immunity. Innate immunity comprises both cellular and humoral components, the humoral arm consisting of pattern recognition molecules such as complement C1q, collectins and ficolins. These molecules activate the complement cascade, neutralize pathogens, and recruit antigen presenting cells. Here we review the current understanding of anti-viral components of the humoral innate immune system that play a similar role to antibodies, describing their role in immunity to HCV and their potential contribution to HCV pathogenesis.

| S-EPMC3280516 | biostudies-literature

Mucosal IgA & IL-1? in Helicobacter pylori Infection.

Project description:Helicobacter pylori infection stimulates strong local inflammatory and specific IgA antibody production. The influence of antibodies on the bacterial colonization is not clear. Here, we have analysed the association between the mucosal IgA level and IL-1? in various manifestations of the infection seen endoscopically. Antral biopsies of 57 dyspeptic patients were taken for culture, histology and estimation of mucosal levels of anti-H. pylori IgA and IL-1?. Mean mucosal IgA level was higher in patients with normal mucosa compared to all other groups and lower IgA level was associated with higher bacterial density. IL-1? was higher in ulcer patients and suspicious malignancy group as compared to normal group and higher level of IL-1? was associated with higher grades of metaplasia. Present study indicates that local immunity seems to have a protective role against H. pylori infection and higher level of IL-1? induced by the pathogen may be associated with metaplasia and carcinogenesis.

| S-EPMC3547450 | biostudies-literature

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