Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila

Ji-Hwan Ryu et al. 2008. Science 319: 777-782.

Speaker: Yu-Lun Cheng (鄭宇倫)                                           Time: 14:00~15:00, May. 7, 2008

Commentator: Jyh-Wei Shin, Ph.D.（辛致煒老師）                    Place: Room 601

Abstract:

        In many animals, gut microbiota exists in the host gut and influence host physiology. Many in vitro evidences demonstrate the relationship between gut micobiota and host immunity, but there is no animal model to analyze molecular interaction. In 2003, authors found the homeobox geneCaudal (Cad) which regulates constitutive local expression of anti-microbial peptide (AMP) gene in Drosophila epithelia (1). In this paper, authors study how commensal microbiota interacts with Drosophila gut to influence host innate immunity by Cad. First of all, it was proof that commensal microbes of the gut can chronically induce a high level of local IMD pathway activation in conventionally reared flies (CR flies). Then, the expression of AMPs are not repressed through IMD pathway in CR^Cad-RNAi flies (specific-Cad RNAi in CR flies). Besides, the percentage of apoptotic cells increases in the gut of the CR^Cad-RNAi flies compared to CR^cont flies. Next, authors isolated and identified five strains of commensal microbes from wild type CR flies. In the CR^Cad-RNAi flies, the numbers of G707 strain increase and the numbers of A911 strain, which are sensitive to Cecropin A1 (AMPs), decrease in the gut. According survival rate survey, germ-free flies (GF flies) do not survive by oral infection with G707 strain. However, the numbers of G707 strain decrease when A911 strain exists in the gut. It is that the presence of A911 strain is sufficient to prevent G707 strain dominance. Last, the restoration of Cad expression in CR^Cad-RNAi flies can recover the same levels of apoptotic cells, AMP expression, flies survival rate, and commensal microbes community. Summaries of the all, Cad can repress the expression of AMPs though IMD pathway. When Cad is knockdown not to repress the expression of AMPs, AMPs react with A911 strain. Decreased A911 strain does not prevent G707 strain from gut pathology. The results elucidate the linkage between the immune genotype–based commensal community structure and host physiology. It also provides important insights into the causative role of pathogenic commensal microbes in chronic inflammatory diseases of the commensal-contacting epithelia.

References:

1.      Ryu, J. H. et al. 2003. The homeobox gene Caudal regulates constitutive local expression of antimicrobial peptide genes in Drosophila epithelia. Mol. Cell. Biol. 24: 172-185.