Humoral immunity in the gut selectively targets phenotypically virulent attaching-and-effacing bacteria for intraluminal elimination

Nobuhiko Kamada, Kei Sakamoto, Sang Uk Seo, Melody Y. Zeng, Yungi Kim, Marilia Cascalho, Bruce A. Vallance, José L. Puente, Gabriel Núñez

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)617-627
Number of pages11
JournalCell Host and Microbe
Volume17
Issue number5
DOIs
Publication statusPublished - 2015 May 13
Externally publishedYes

Fingerprint

Citrobacter rodentium
Humoral Immunity
Virulence Factors
Bacteria
Virulence
Diethylpropion
Intestinal Diseases
Microbiota
Enterobacteriaceae
Infection
Antibody Formation
Immune System
Immunity
Neutrophils
Down-Regulation
Epithelium
Immunoglobulin G
Gene Expression
Survival
Antibodies

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Humoral immunity in the gut selectively targets phenotypically virulent attaching-and-effacing bacteria for intraluminal elimination. / Kamada, Nobuhiko; Sakamoto, Kei; Seo, Sang Uk; Zeng, Melody Y.; Kim, Yungi; Cascalho, Marilia; Vallance, Bruce A.; Puente, José L.; Núñez, Gabriel.

In: Cell Host and Microbe, Vol. 17, No. 5, 13.05.2015, p. 617-627.

Research output: Contribution to journalArticle

Kamada, Nobuhiko ; Sakamoto, Kei ; Seo, Sang Uk ; Zeng, Melody Y. ; Kim, Yungi ; Cascalho, Marilia ; Vallance, Bruce A. ; Puente, José L. ; Núñez, Gabriel. / Humoral immunity in the gut selectively targets phenotypically virulent attaching-and-effacing bacteria for intraluminal elimination. In: Cell Host and Microbe. 2015 ; Vol. 17, No. 5. pp. 617-627.
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