25-hydroxycholesterol: Gatekeeper of intestinal IgA

ABSTRACT Studies utilizing various immunodeficient mouse models of rotavirus (RV) infection demonstrated significant roles of RV-specific secretory immunoglobulin A (IgA), CD4+ T cells, and CD8+T cells in the clearance of RV and protection from secondary infection. Secretion of small but detectable amounts of IgA in RV-infected αβ T-cell receptor knockout mice (11) and distinctive anatomical localization and physiology of B1 cells suggested that B1 cells might be capable of producing RV-specific intestinal IgA in a T-cell-independent fashion and, therefore, be responsible for ablation of RV shedding. We investigated the role of B1 cells in the resolution of primary RV infection using a SCID mouse model. We found that the adoptive transfer of unseparated peritoneal exudate cells ablates RV shedding and leads to the production of high levels of RV-specific intestinal IgA. In contrast, purified B1 cells do not ablate RV shedding and do not induce a T-cell-independent or T-cell-dependent, RV-specific IgA response but do secrete large amounts of polyclonal (total) intestinal IgA. Cotransfer of mixtures of purified B1 cells and B1-cell-depleted peritoneal exudate cells differing in IgA allotypic markers also demonstrated that B2 cells (B1-cell-depleted peritoneal exudate cells) and not B1 cells produced RV-specific IgA. To our knowledge, this is the first observation that B1 cells are unable to cooperate with CD4+ T cells and produce virus-specific intestinal IgA antibody. We also observed that transferred CD4+ T cells alone are capable of resolving RV shedding, although no IgA is secreted. These data suggest that RV-specific IgA may not be obligatory for RV clearance but may protect from reinfection and that effector CD4+ T cells alone can mediate the resolution of primary RV infection. Reconstitution of RV-infected SCID mice with B1 cells results in the outgrowth of contaminating, donor CD4+ T cells that are unable to clear RV, possibly because their oligoclonal specificities may be ineffective against RV antigens.

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Effect of hyperoxia on the intestinal IgA secretory component in neonatal rats and on intestinal epithelial cells in vitro

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x2010007500106 ◽

2010 ◽

Vol 43 (11) ◽

pp. 1034-1041 ◽

Cited By ~ 9

Author(s):

D.Y. Liu ◽

J.J. Li

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Secretory Component ◽

Intestinal Epithelial ◽

Neonatal Rats ◽

Intestinal Iga

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IgA dysfunction induced by the early-lifetime disruption of gut microbiota aggravates diet–induced metabolic syndrome in mice

10.21203/rs.3.rs-40336/v2 ◽

2021 ◽

Author(s):

Jielong Guo ◽

Xue Han ◽

Yilin You ◽

Weidong Huang ◽

Zhan Jicheng

Keyword(s):

Metabolic Syndrome ◽

Gut Microbiota ◽

Early Life ◽

Low Dose ◽

Dependent Manner ◽

Wild Type ◽

Bacterial Composition ◽

Germ Free ◽

Iga Response ◽

Intestinal Iga

Abstract BackgroundLow-dose antibiotic contamination in animal food is still a severe food safety problem worldwide. Penicillin is one of the main classes of antibiotics being detected in food. Previous studies have shown that transient exposure of low-dose penicillin (LDP) during early life resulted in metabolic syndrome (MetS) in mice. However, the underlying mechanism(s) and efficient approaches to counteracting this are largely unknown.MethodsWild-type (WT) or secretory IgA (SIgA)-deficient (Pigr-/-) C57BL/6 mice were exposed to LDP or not from several days before birth to 30 d of age. Five times of FMT or probiotics (a mixture of Lactobacillus bulgaricus and L. rhamnosus GG) treatments were applied to parts of these LDP-treated mice from 12 d to 28 d of life. Bacterial composition from different regions (mucosa and lumen) of the colon and ileum were analyzed through 16S rDNA sequencing. Intestinal IgA response was analyzed. Multiple parameters related to MetS were also determined. In addition, germ-free animals and in vitro tissue culture were also used to determine the correlations between LDP, gut microbiota (GM) and intestinal IgA response.ResultsLDP disturbed the intestinal bacterial composition, especially for ileal mucosa, the main inductive and effective sites of IgA response, in 30-d-old mice. The alteration of early GM resulted in a persistent inhibition of the intestinal IgA response, leading to a constant reduction of fecal and caecal SIgA levels throughout the 25-week experiment, which is early life-dependent, as transfer of LDP-GM to 30 d germ-free mice only resulted in a transient reduction in fecal SIgA. LDP-induced reduction in SIgA led to a decrease in IgA+ bacteria and a dysbiosis in the ileal mucosal samples of 25 week wild-type but not Pigr-/- mice. Moreover, LDP also resulted in increases in ileal bacterial encroachment and adipose inflammation, along with an enhancement of diet-induced MetS in an intestinal SIgA-dependent manner. Furthermore, several times of FMT or probiotic treatments during LDP treatment are efficient to fully (for FMT) or partially (for probiotics) counteract the LDP-effect on both GM and metabolism.ConclusionsEarly-life LDP-induced enhancement of diet-induced MetS is mediated by intestinal SIgA, which could be (partially) restored by FMT or probiotics treatment.

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