Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.
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.
Ryu
Ji-Hwan
JH
Division of Molecular Life Science, Ewha Woman's University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.
Kim
Sung-Hee
SH
Lee
Hyo-Young
HY
Bai
Jin Young
JY
Nam
Young-Do
YD
Bae
Jin-Woo
JW
Lee
Dong Gun
DG
Shin
Seung Chul
SC
Ha
Eun-Mi
EM
Lee
Won-Jae
WJ
D016947:Acetobacteraceae / Q000254:growth & development; D000818:Animals; D030801:Animals, Genetically Modified; D000898:Antibiosis; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis; D001419:Bacteria / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D017344:Genes, Insect; D005856:Germ-Free Life; D020576:Gluconobacter / Q000254:growth & development* / Q000472:pathogenicity; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006706:Homeostasis; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D034622:RNA Interference; D013559:Symbiosis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C101626:Rel protein, Drosophila; D014157:Transcription Factors; C084564:cad protein, Drosophila