Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism

TLDR

The gut harbors trillions of bacteria that remain immunologically silent through compartmentalization mediated by pattern‑recognition receptors such as Toll‑like receptors, and loss of this segregation could provoke immune activation. The study investigates whether disrupting gut compartmentalization triggers an immune response to resident bacteria. Toll‑like receptor signaling is essential for keeping bacteria compartmentalized; without it, bacteria spread systemically and elicit a strong antibody response that, despite breaking systemic ignorance, still allows tolerance and preserves host‑microbiota mutualism. Citation: Slack et al.

Abstract

Maintaining Mutual Ignorance Our gut is colonized by trillions of bacteria that do not activate the immune system because of careful compartmentalization. Such compartmentalization means that our immune system is “ignorant” of these microbes and thus it has been proposed that loss of compartmentalization might result in an immune response to the colonizing bacteria. Microorganisms are sensed by cells that express pattern recognition receptors, such as Toll-like receptors, which recognize patterns specific to those microbes. Slack et al. (p. 617 ) show that Toll-like receptor–dependent signaling is required to maintain compartmentalization of bacteria to the gut of mice. In the absence of Toll-dependent signaling, intestinal bacteria disseminated throughout the body and the mice mounted a high-titer antibody response against them. This antibody response was of great functional importance because, despite the loss of systemic ignorance to intestinal microbes, the mice were tolerant of the bacteria. Thus, in the absence of innate immunity, the adaptive immune system can compensate so that host and bacterial mutualism can be maintained.