Interactions between commensal intestinal bacteria and the immune system

Abstract

Although we might shudder at the thought of billions of bacteria living in our lower intestine, we are colonized by these passengers shortly after birth. However, the relationship is mostly of mutual benefit, and they shape our immune system throughout life. Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity and their relevance to the effects of hygiene on human disease.

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Figure 1: Keeping germ-free mice in an isolator.
Figure 2: The presence of intestinal bacteria has a large impact on lymphoid structures of both the intestine and systemic tissues.
Figure 3: Immune defences against commensal intestinal bacteria.

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Correspondence to Andrew J. Macpherson.

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DATABASES

Entrez Gene

CD4

CD8

CD25

CD45

Fas

FOXP3

IL-10

interferon-γ

TIM1

transforming growth factor-β1

Glossary

DEFENSINS

A family of proteins exhibiting bactericidal properties. They are secreted by immune cells (particularly neutrophils), intestinal Paneth cells and epithelial cells.

EXHAUSTION

Non-responsiveness of the immune system resulting from the deletion of specific thymocytes (central tolerance) and the deletion or functional inactivation of specific T cells in the periphery (peripheral tolerance) in the presence of large quantities of antigen.

IGNORANCE

Non-responsiveness of the immune system in the presence of a given antigen, despite the existence of specific T and B cells capable of mounting a functional response.

INFLAMMATORY BOWEL DISEASE

Immune-mediated inflammation of the bowel. There are two main forms: Crohn's disease, which is a granulomatous segmental inflammation affecting any part of the intestine, and ulcerative colitis, which is a mucosal inflammation involving the rectum and extending for a variable distance along the colon. In developed countries, the incidence of inflammatory bowel disease is approximately 1 in 50,000. It usually starts in early adult life and continues afterwards with a relapsing, remitting course.

LAMINA PROPRIA

The layer of the intestine between the epithelial cells and the most superficial smooth-muscle layer.

MIMICRY

Resemblance between epitopes contained within microbial and host proteins, leading to crossreactivity of T cells in the host.

MUTUALISM

The relationship between two different species that live in close proximity and benefit from one another.

PEYER'S PATCHES

Collections of lymphoid tissue located in the mucosa of the small intestine, with an outer epithelial layer containing specialized epithelial cells, called M cells.

REPERTOIRE

The spectrum of B or T cells. Defined according to the specificities of the B-cell- or T-cell-receptors that are present immediately before onset of a clinically important infection.

T-CELL-DEPENDENT ANTIGEN

To generate an antibody response to a T-cell-dependent protein antigen requires recognition of the antigen (in the context of MHC molecules) by helper T cells and cooperation between those antigen-specific T cells and B cells that recognize the same antigen.

TOLL-LIKE RECEPTORS

Cell-associated pattern-recognition receptors that recognize molecules unique to microorganisms, resulting in immune-cell activation and production of pro-inflammatory molecules.

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Macpherson, A., Harris, N. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478–485 (2004). https://doi.org/10.1038/nri1373

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