Medical College of Wisconsin
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Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection. Cell Host Microbe 2021 Dec 08;29(12):1744-1756.e5

Date

10/23/2021

Pubmed ID

34678170

Pubmed Central ID

PMC8667605

DOI

10.1016/j.chom.2021.09.010

Scopus ID

2-s2.0-85117839880 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

Interactions between the microbiota and mammalian host are essential for defense against infection, but the microbial-derived cues that mediate this relationship remain unclear. Here, we find that intestinal epithelial cell (IEC)-associated commensal bacteria, segmented filamentous bacteria (SFB), promote early protection against the pathogen Citrobacter rodentium, independent of CD4+ T cells. SFB induced histone modifications in IECs at sites enriched for retinoic acid receptor motifs, suggesting that SFB may enhance defense through retinoic acid (RA). Consistent with this, inhibiting RA signaling suppressed SFB-induced protection. Intestinal RA levels were elevated in SFB mice, despite the inhibition of mammalian RA production, indicating that SFB directly modulate RA. Interestingly, RA was produced by intestinal bacteria, and the loss of bacterial-intrinsic aldehyde dehydrogenase activity decreased the RA levels and increased infection. These data reveal RA as an unexpected microbiota-derived metabolite that primes innate defense and suggests that pre- and probiotic approaches to elevate RA could prevent or combat infections.

Author List

Woo V, Eshleman EM, Hashimoto-Hill S, Whitt J, Wu SE, Engleman L, Rice T, Karns R, Qualls JE, Haslam DB, Vallance BA, Alenghat T

Author

Emily M. Eshleman PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bacillus cereus
Bacteria
Bifidobacterium bifidum
CD4-Positive T-Lymphocytes
Citrobacter rodentium
Epithelial Cells
Histone Code
Intestinal Diseases
Male
Mice
Mice, Inbred C57BL
Microbiota
Nitric Oxide
Signal Transduction
Symbiosis
Tretinoin