Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Srivastava R

PROVIDER: S-EPMC3547450 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Srivastava Ragini R Kashyap Antara A Kumar Mohan M Nath Gopal G Jain Ashok Kumar AK

Indian journal of clinical biochemistry : IJCB 20120926 1

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-1β 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-1β. Mean mucosal IgA level was higher in pa ...[more]

PMID: 24381416

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Project description:BackgroundOngoing Helicobacter pylori (HP) infection triggers a chronic active gastritis. Eradicating HP reduces gastric inflammation, but does not eliminate it. We sought to characterize this persistent gastritis, and demonstrate the persistence of HP-specific Th17 responses in individuals previously infected with HP but who no longer had evidence of ongoing infection.Methodology/principal findingsStudy subjects were divided into 3 groups 55 individuals had active HP infection (group A), 41 were diagnosed with previous HP infection (group P), and 59 were naïve to HP (group N). Blood and gastric tissue were obtained with written informed consent from all subjects, and immune responses were evaluated using flow cytometry, semi-quantitative real time PCR, immunofluorescent staining, ELISA, and multiplex cytometric bead array for cytokine quantification. Elevated IL-17A responses were observed in patients from group A compared to group N. Interestingly, IL-17A responses remained persistently elevated in the blood and gastric mucosa of individuals from group P, despite the absence of ongoing HP infection. Using purified CD4(+) T cells as effectors and antibodies that blocked antigen presentation by MHC Class II, we showed that these persistent IL-17A responses were mediated primarily by HP-specific Th17 cells, rather than other immune cells that have also been described to secrete IL-17A. Gastric mucosal IL-1? levels were also persistently elevated in group P, and neutralisation of IL-1? reduced the HP-specific IL-17A response of purified CD4(+) T cells to autologous HP-pulsed antigen presenting cells in vitro, suggesting a functional association between IL-1? and the persistent Th17 response in group P patients.Conclusions/significanceDespite lack of ongoing HP infection, HP-specific Th17 cells persist in the blood and gastric mucosa of individuals with past HP infection. We speculate that this persistent inflammation might contribute to gastric mucosal pathology, for example, persistent increased gastric cancer risk despite eradication of HP.

Project description:T helper (Th) cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE)-based and agent-based modeling (ABM) to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP) in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg) cells. We also investigated the potential role of peroxisome proliferator-activated receptor ? (PPAR?) activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPAR? knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches characterized the induction of mucosal effector and regulatory pathways controlled by PPAR? during H. pylori infection affecting disease outcomes.

Dataset Information

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

Publications

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

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