How does the microbiota control systemic innate immunity?

Jordan, Christine K. I.; Clarke, Thomas B.

doi:10.1016/j.cell.2024.03.036

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Jordan, C. K. I., & Clarke, T. B. (2024). How does the microbiota control systemic innate immunity? Trends in Immunology, 45(2), 2030–2051.
Added by: Dr. Enrique Feoli (12/06/2025, 17:09) Last edited by: Dr. Enrique Feoli (12/06/2025, 17:18)

Resource type: Journal Article
DOI: 10.1016/j.cell.2024.03.036
ID no. (ISBN etc.): 928674
BibTeX citation key: Jordan2024
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Categories: BioAcyl Corp
Subcategories: Microbiota on immunity
Keywords: infection, microbiota, systemic innate immunity
Creators: Clarke, Jordan
Publisher: Cell Press
Collection: Trends in Immunology

Views: 2/17

Abstract

Significance

Humans form lifelong associations with microbial communities, the most influential being the intestinal microbiota. Once believed to impact only their gut niche, intestinal microbes are now known to influence nearly all aspects of physiology. The primary benefit of this is programming systemic immunity to protect against infection. Understanding how intestinal microbes integrate into physiology promises to reveal not only how mammals form symbiotic partnerships with microbes but also new putative treatments for infection through microbiota manipulation.

Highlights

Symbiotic microbes in the gut can control immune development and host defenses systemically.

While there are no live microbial communities in non-mucosal systemic tissues, nearly all host tissues are bathed in a multitude of immunologically active microbial products.

We are only just beginning to understand which members of the gut microbiota can control systemic immunity.

The systemic effects of gut microbes need to be controlled to avoid systemic immunopathology.

Gut microbes might be used to manipulate systemic immunity; to achieve this, we posit that a deeper understanding of how gut microbes communicate with peripheral tissues is essential.

Abstract

The intestinal microbiota has a pervasive influence on mammalian innate immunity fortifying defenses to infection in tissues throughout the host. How intestinal microbes control innate defenses in systemic tissues is, however, poorly defined. In our opinion, there are three core challenges that need addressing to advance our understanding of how the intestinal microbiota controls innate immunity systemically: first, deciphering how signals from intestinal microbes are transmitted to distal tissues; second, unraveling how intestinal microbes prime systemic innate immunity without inducing widespread immunopathology; and third, identifying which intestinal microbes control systemic immunity. Here, we propose answers to these problems which provide a framework for understanding how microbes in the intestine can regulate innate immunity systemically.

Notes

Depicted are infections where signals from the gut have been shown to enhance host defenses beyond the gut. Pathogens are listed below the models of infection used. Immune cells that are programmed by signals from intestinal microbes are indicated. While there are further studies that indicate that the microbiota enhances resistance to infection outside the gut, here we include only infections where there is evidence that signals from intestinal microbes are important in regulating immune defenses. These findings are derived from various mouse models. See text for references. Abbreviations: DC, dendritic cell; Mθ, alveolar macrophage; pDC, plasmacytoid dendritic cell. Hepatitis virus is mouse hepatitis virus. This figure was created using BioRender.com.