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Publication : Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection.

First Author  Woo V Year  2021
Journal  Cell Host Microbe Volume  29
Issue  12 Pages  1744-1756.e5
PubMed ID  34678170 Mgi Jnum  J:321941
Mgi Id  MGI:6874696 Doi  10.1016/j.chom.2021.09.010
Citation  Woo V, et al. (2021) Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection. Cell Host Microbe 29(12):1744-1756.e5
abstractText  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.
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