Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination.
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.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: nkamada@umich.edu.
Nobuhiko
N
Kamada
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kei
K
Sakamoto
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sang-Uk
SU
Seo
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Melody Y
MY
Zeng
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yun-Gi
YG
Kim
Department of Surgery and Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Marilia
M
Cascalho
Division of Gastroenterology, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
Bruce A
BA
Vallance
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
José L
JL
Puente
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: gabriel.nunez@umich.edu.
Gabriel
G
Núñez
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D044082:Citrobacter rodentium / Q000254:growth & development* / Q000276:immunology*; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D014774:Virulence; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D037521:Virulence Factors