TY - JOUR
T1 - Humoral immunity in the gut selectively targets phenotypically virulent attaching-and-effacing bacteria for intraluminal elimination
AU - Kamada, Nobuhiko
AU - Sakamoto, Kei
AU - Seo, Sang Uk
AU - Zeng, Melody Y.
AU - Kim, Yun Gi
AU - Cascalho, Marilia
AU - Vallance, Bruce A.
AU - Puente, José L.
AU - Núñez, Gabriel
N1 - Funding Information:
The authors thank the University of Michigan Germ-free Animal Core, Microscopy and Image Analysis Laboratory , the Center for Molecular Imaging, and Flow Cytometry Core for support; Grace Chen for review of the manuscript; Jenna Rousseau for technical assistance and Alison O’Brien for providing E. coli expressing Intimin. B.A.V. is the CH. I.L.D. Foundation Chair in Pediatrics IBD Research. This work was supported by a Career Development Award from the Crohn’s and Colitis Foundation of America (to N.K. and Y.-G.K.); Michigan Gastrointestinal Peptide Research Center NIDDK 5P30DK034933 (N.K.); Grant-in-Aid for Japan Society for the Promotion of Science Fellows , Kanae Foundation for the Promotion of Medical Science , and Mishima Kaiun Memorial Foundation (K.S.); NIH Training Grant T32DK094775 (to M.Y.Z.), grants from the NIH DK095782 ; and the Bill & Melinda Gates Foundation (G.N.). The authors declare no competing financial interests.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/13
Y1 - 2015/5/13
N2 - Virulence factors expressed by enteric bacteria are pivotal for pathogen colonization and induction of intestinal disease, but the mechanisms by which host immunity regulates pathogen virulence are largely unknown. Here we show that specific antibody responses are required for downregulation of virulence gene expression in Citrobacter rodentium, an enteric pathogen that models human infections with attaching-and-effacing bacteria. In the absence of antibodies against the pathogen, phenotypically virulent C. rodentium, accumulated and infected the epithelium and subsequently invaded the lamina propia, causing host lethality. IgG induced after infection recognized virulence factors and bound virulent bacteria within the intestinal lumen, leading to their engulfment by neutrophils, while phenotypically avirulent pathogens remained in the intestinal lumen and were eventually outcompeted by the microbiota. Thus, the interplay of the innate and adaptive immune system selectively targets virulent C. rodentium in the intestinal lumen to promote pathogen eradication and host survival.
AB - Virulence factors expressed by enteric bacteria are pivotal for pathogen colonization and induction of intestinal disease, but the mechanisms by which host immunity regulates pathogen virulence are largely unknown. Here we show that specific antibody responses are required for downregulation of virulence gene expression in Citrobacter rodentium, an enteric pathogen that models human infections with attaching-and-effacing bacteria. In the absence of antibodies against the pathogen, phenotypically virulent C. rodentium, accumulated and infected the epithelium and subsequently invaded the lamina propia, causing host lethality. IgG induced after infection recognized virulence factors and bound virulent bacteria within the intestinal lumen, leading to their engulfment by neutrophils, while phenotypically avirulent pathogens remained in the intestinal lumen and were eventually outcompeted by the microbiota. Thus, the interplay of the innate and adaptive immune system selectively targets virulent C. rodentium in the intestinal lumen to promote pathogen eradication and host survival.
UR - http://www.scopus.com/inward/record.url?scp=84929356648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929356648&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.04.001
DO - 10.1016/j.chom.2015.04.001
M3 - Article
C2 - 25936799
AN - SCOPUS:84929356648
SN - 1931-3128
VL - 17
SP - 617
EP - 627
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -
