Segmented Filamentous Bacterium Uses Secondary and Tertiary Lymphoid Tissues to Induce Gut IgA and Specific T Helper 17 Cell Responses

Abstract

Segmented filamentous bacterium (SFB) is a symbiont that drives postnatal maturation of gut adaptive immune responses. In contrast to nonpathogenic E. coli, SFB stimulated vigorous development of Peyer's patches germinal centers but paradoxically induced only a low frequency of specific immunoglobulin A (IgA)-secreting cells with delayed accumulation of somatic mutations. Moreover, blocking Peyer's patch development abolished IgA responses to E. coli, but not to SFB. Indeed, SFB stimulated the postnatal development of isolated lymphoid follicles and tertiary lymphoid tissue, which substituted for Peyer's patches as inductive sites for intestinal IgA and SFB-specific T helper 17 (Th17) cell responses. Strikingly, in mice depleted of gut organized lymphoid tissue, SFB still induced a substantial but nonspecific intestinal Th17 cell response. These results demonstrate that SFB has the remarkable capacity to induce and stimulate multiple types of intestinal lymphoid tissues that cooperate to generate potent IgA and Th17 cell responses displaying only limited target specificity.

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

“…In rodents, SFB colonization leads to robust germinal center (GC) B-cell responses in the Peyer's patches and the subsequent accumulation of T-cell-dependent IgA-producing plasma cells in the SI-LP (28,29). Additionally, Th17 cells promote IgA class switching in the Peyer's patches (30).…”

When pathogenic bacteria meet the intestinal microbiota

“…An example of a member of the microbiota that contributes to the immune system development is Bacteroides fragilis, with the demonstration that monocolonization of germ-free mice with this bacterium is sufficient to promote the development of CD4T lymphocytes [37]. Similarly, segmented filamentous bacteria have been described to be sufficient to drive the differentiation of CD4T cells into Th17 cells, important for protection against the intestinal pathogen C. rodentium [38][39][40][41]. The intestinal microbiota is also an inexhaustible source of ligands for the innate immune system.…”

Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens?

“…IgA also generally limits intestinal bacterial overgrowth (Wei et al 2011). Generally, those taxa that are the most likely to generate intestinal inflammation are also the more strongly targeted by secreted Ig (Lecuyer et al 2014;Palm et al 2014;Bunker et al 2015). Nevertheless, these responses to benign microbes are mainly focused on the intestinal mucosa, unless the intestinal permeability barrier is breached and the live organism reaches systemic secondary lymphoid structures (Macpherson et al 2000;Konrad et al 2006).…”