Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice.
Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminth Heligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacterium Citrobacter rodentium infection, BALB/c and STAT 6 knockout (KO) mice were infected with H. polygyrus, C. rodentium, or both. We found that only BALB/c mice coinfected with H. polygyrus and C. rodentium displayed a marked morbidity and mortality. The enhanced susceptibility to C. rodentium and intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition, C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promote C. rodentium infection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude that H. polygyrus coinfection can promote C. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.
Chen
Chien-Chang
CC
Chang Gung University and Chang Gung Children's Hospital, Taoyuan, Taiwan.
Louie
Steve
S
McCormick
Beth
B
Walker
W Allan
WA
Shi
Hai Ning
HN
D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology / Q000473:pathology; D005243:Feces / Q000382:microbiology; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D050800:STAT6 Transcription Factor; D017206:Strongylida Infections / Q000276:immunology* / Q000401:mortality; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics
D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators