Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination.

TitleHumoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination.
Publication TypeJournal Article
Year of Publication2015
AuthorsKamada N, Sakamoto K, Seo S-U, Zeng MY, Kim Y-G, Cascalho M, Vallance BA, Puente JL, Nunez G
JournalCell Host Microbe
Volume17
Issue5
Pagination617-27
Date Published2015 May 13
ISSN1934-6069
KeywordsAnimals, Antibodies, Bacterial, Citrobacter rodentium, Disease Models, Animal, Enterobacteriaceae Infections, Gastrointestinal Tract, Immunity, Humoral, Immunoglobulin G, Mice, Inbred C57BL, Neutrophils, Phagocytosis, Virulence, Virulence Factors
Abstract

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.

DOI10.1016/j.chom.2015.04.001
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https://www.ncbi.nlm.nih.gov/pubmed/25936799?dopt=Abstract

Alternate JournalCell Host Microbe
PubMed ID25936799
PubMed Central IDPMC4433422
Grant ListP30 CA046592 / CA / NCI NIH HHS / United States
T32DK094775 / DK / NIDDK NIH HHS / United States
T32 HL007517 / HL / NHLBI NIH HHS / United States
5P30DK034933 / DK / NIDDK NIH HHS / United States
P30 DK034933 / DK / NIDDK NIH HHS / United States
R01 DK095782 / DK / NIDDK NIH HHS / United States
T32 DK094775 / DK / NIDDK NIH HHS / United States
NIH DK095782 / DK / NIDDK NIH HHS / United States

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