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Commensals shape the immune system

Nature Reviews Immunology volume 21, page 615 (2021)Cite this article

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At the turn of the millennium, it was known that germ-free animals have an immature immune system, with reduced lymphoid tissue, fewer immune cells and decreased immune responsiveness. However, the identity of the commensal bacteria capable of stimulating immune maturation was elusive and the molecular mechanisms unclear.

A 2005 landmark paper by Mazmanian et al. initiated the molecular and genetic characterization of the immune–microflora crosstalk. The study identified a microbial species, Bacteroides fragilis, that produces a defined molecule, polysaccharide A (PSA), that acts on dendritic cells (DCs) to stimulate TH1-type immunity and consequent lymphoid organogenesis. The process depended on physical interaction between PSA and intestinal DCs, DC expression of MHC-II and their production of IL-12. Monocolonization with B. fragilis or gastric administration of purified PSA to gnotobiotic mice was sufficient to stimulate CD4+ T cell expansion, whereas a PSA-deficient B. fragilis mutant was unable to do so. This work elegantly demonstrated that PSA was sufficient to drive aspects of immune maturation.

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References

Original article

  • Mazmanian, S. K. et al. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005)

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Authors and Affiliations

  1. Gustave Roussy Cancer Campus, Villejuif, France

    Laurence Zitvogel & Guido Kroemer

Authors
  1. Laurence Zitvogel
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  2. Guido Kroemer
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Corresponding author

Correspondence to Guido Kroemer.

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Competing interests

L.Z. holds patents dealing with the intestinal microbiota and its manipulation for cancer treatment. L.Z. and G.K. are co-founders of everImmune.

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Zitvogel, L., Kroemer, G. Commensals shape the immune system. Nat Rev Immunol 21, 615 (2021). https://doi.org/10.1038/s41577-021-00606-y

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