Microbiota and immunity

Gérard EBERL, Team leader
Rute MARQUES, Postdoc
Grégoire CHEVALIER, Postdoc
Sophie DULAUROY, Technician
Lucette POLOMACK, Technician

Symbiotic microbiota and the development of the immune system



The symbiotic microbiota plays an essential role at many levels of host physiology, and germfree mice develop a large number of defects. In the intestine, the microbiota metabolises nutrients and toxins to generate an output that provides the hosts with vital compounds. The microbiota also regulates tissue homeostasis, provides protection against pathogens and affects the development and activation of the intestinal and systemic immune system. We have shown how compounds shed by the intestinal microbiota activates a cascade of signaling events that leads to the activation of intestinal LTi cells, the activation of stromal cells, the recruitment of B cells, and the formation of hundreds of tertiary lymphoid tissues involved in intestinal homeostasis. The intestinal microbiota also modulates the activity of RORgt+ ILCs and is required for the differentiation of Th17 cells. We aim at understanding how the symbiotic microbiota affects the development and activation of pro-inflammatory immunity in particular, and of intestinal and systemic immunity in general, in order to establish a functional interactome between the microbiota, the immune system and the host.

A cryptopatch (left, 400x) and an ILF (right, 100x) in mouse adult intestine. LTi cells (green), DCs (red) and B cells (blue).
Symbiotic bacteria induce the formation of ILFs from cryptopatches (Bouskra et al., Nature 2008).

The mechanism by which Gram-megative symbiotic bacteria induce the formation of ILFs from cryptopatches. To divide, bacteria have to break down their cell wall, thereby releasing peptidoglycans recognized by pattern recognition receptors, such as NOD1. This triggers a cascade of events that culminates in the generation of IgA+ B cells by ILFs and the establishment of a negative feedback loop on the bacterial population. Such a negative feedback loop is set to maintain intestinal homeostasis (Eberl and Lochner, Mucosal Immunol. 2009).

More generally, we have discussed the notion that the host and its symbiotic microbiota constitutes a superorganism endowed with optimal performances: intestinal bacteria increase our capacity to extract energy from food. In the intestine and other niches, such as vagina and skin, the microbiota establishes an ecosystem that protects the niche from invaders, and the host from pathogens. We have proposed that the relationship between host and microbes is best described by a continuum of types of interactions, rather than a dualistic confrontation between mutualists and regulatory immunity on the one hand, and pathogens and pro-inflammatory immunity on the other hand.

The immune system is a major force to maintain homeostasis betwween the host and its symbiotic microbiota, constituting a functional superorganism. A continuum of types of microbes face a continuum of types of immune responses in a dynamic process of constant adaptation (Eberl, Mucosal Immunol. 2010)