Martina Sassone-Corsi

Conference 2023 Live Talk

Talk title

Modulation of intestinal T cell responses by a commensal microbe

Authors and Affiliations

Martina Sassone-Corsi1, Shalhevet Azriel2, Ariel Simon2, Deepshika Ramanan1, Adriana Ortiz-Lopez1, Felicia Chen1, Nissan Yissachar2, Diane Mathis1, Christophe Benoist1

1. Department of Immunology, Harvard Medical School, Boston, MA 02115.
2. Goodman Faculty of Life Sciences, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Abstract

Background

T cells that express the transcription factor RORγ, regulatory (Treg), or conventional (Th17) are strongly influenced by intestinal symbionts.

Methods

In a genetic approach to identify mechanisms underlying this influence, we performed a screen for microbial genes implicated, in germfree mice monocolonized with Escherichia coli Nissle.

Results

The loss of capsule-synthesis genes impaired clonal expansion and differentiation of intestinal RORγ+ T cells. Mechanistic exploration revealed that the capsule-less mutants remained able to induce species-specific immunoglobulin A (IgA) and were highly IgA-coated. They could still trigger myeloid cells, and more effectively damaged epithelial cells in vitro. Unlike wild-type microbes, capsule-less mutants were mostly engulfed in intraluminal casts, large agglomerates composed of myeloid cells extravasated into the gut lumen.

Conclusions

We speculate that sequestration in luminal casts of potentially harmful microbes, favored by IgA binding, reduces the immune system’s actual exposure, preserving host-microbe equilibrium. The variable immunostimulation by microbes that has been charted in recent years may not solely be conditioned by triggering molecules or metabolites but also by physical limits to immune system exposure.