IgA facilitates the persistence of the mucosal pathogen Helicobacter pylori
OPEN ACCESS
Loading...
Author / Producer
Date
2024-02
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
IgA antibodies have an important role in clearing mucosal pathogens. In this study, we have examined the contribution of IgA to the immune control of the gastrointestinal bacterial pathogens Helicobacter pylori and Citrobacter rodentium. Both bacteria trigger a strong local IgA response that results in bacterial IgA coating in mice and in gastritis patients. Class switching to IgA depends on Peyer’s patches, T-cells, eosinophils, and eosinophil-derived TGF-β in both models. In the case of H. pylori, IgA secretion and bacterial coating also depend on a functional bacterial type IV secretion system, which drives the generation of Th17 cells and the IL-17-dependent expression of the polymeric immunoglobulin receptor PIGR. IgA−/− mice are hypercolonized with C. rodentium in all examined tissues, suffer from more severe weight loss and develop more colitis. In contrast, H. pylori is controlled more efficiently in IgA−/− mice than their WT counterparts. The effects of IgA deficiency of the offspring can be compensated by maternal IgA delivered by WT foster mothers. We attribute the improved immune control observed in IgA−/− mice to IgA-mediated protection from complement killing, as H. pylori colonization is restored to wild type levels in a composite strain lacking both IgA and the central complement component C3. IgA antibodies can thus have protective or detrimental activities depending on the infectious agent.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
18 (1)
Pages / Article No.
232 - 247
Publisher
Elsevier
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Mucosal immunity; Innate immune defense; Immunoglobulin class switching; GI tract infections; Immunopathology
Organisational unit
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich