Saturday, March 3, 2018

Specific microbiota species induce serum IgA that protects against sepsis

Some 10 years ago the scientists made observation that microbiota difference between different mouse colonies is responsible for selective TH17 expansion in the gut. Since then, field of immunology was flooded with numerous observations linking gut [and other tissue] microbiota to functional status of immune system.

One such study was recently published in journal Cell Host and Microbe. The researchers observed that serum IgA secreted by bone marrow residing plasma cells (BM PCs) were selectively enriched in mouse colony harboring members of Proteobacteria phylum. More importantly, these serum IgA protected mice during sepsis following gut damage.

Initially, the authors observed that their institute's B6 mouse colony (PENN-SPF) differed from commercial vendor B6 mice in their serum [but not small intestine] IgA status. Co-housing experiment indicated potential involvement of microbiota.

Indeed, 16S ribosomal gene sequencing showed enrichment of Proteobacteria phylum in local mouse colony (and also Deferribacteres).

Serum IgA bound microbiota and sequencing of serum IgA+/IgA- microbiota species confirmed selective enrichment of species within Proteobacteria phylum.

Development of microbiota-specific serum IgA were T cell-dependent.

Finally, serum IgA protected mice against sepsis following gut tissue damage and microbiota invasion (translocation).

In summary, serum IgA, but not intestinal IgA, is produced by bone marrow plasma cells in response to selective microbiota species, mostly from Proteobacteria phylum in mice. These serum IgA could bind microbiota, it developed in a T cell-dependent manner and protected host during gut flora invasion (translocation) in condition such as sepsis. However, it is not clear why serum IgG [in IgA KO mice] could not protect against sepsis in this study since one previous study already showed that serum IgG protected against gram negative bacteria such as E. coli. It is possible that serum IgA and IgG play non-redundant functions by protected against different microbial species.

posted by David Usharauli

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