Innate immune homeostasis by the homeobox gene Caudal and commensal-gut mutualism in Drosophila

Ji Hwan Ryu, Sung Hee Kim, Hyo Young Lee, Young Bai Jin, Young Do Nam, Jin Woo Bae, Gun Lee Dong, Chul Shin Seung, Eun Mi Ha, Won Jae Lee

Research output: Contribution to journalArticlepeer-review

654 Scopus citations

Abstract

Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B-dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.

Original languageEnglish
Pages (from-to)777-782
Number of pages6
JournalScience
Volume319
Issue number5864
DOIs
StatePublished - 8 Feb 2008

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