Helminth-primed dendritic cells alter the host response to enteric bacterial infection.
To examine whether intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established using the intestinal helminth Heligomosomoides polygyrus and a murine pathogen Citrobacter rodentium, which causes infectious colitis. Using this model we recently have shown that coinfection with the Th2-inducing H. polygyrus and C. rodentium promotes bacterial-associated disease and colitis. In this study, we expand our previous observations and examine the hypothesis that dendritic cells (DC) stimulated by helminth infection may play an important role in the regulation of the intestinal immune response to concurrent C. rodentium infection as well as in the modulation of the bacterial pathogenesis. We show that H. polygyrus infection induces DC activation and IL-10 expression, and that adoptive transfer of parasite-primed DC significantly impairs host protection to C. rodentium infection, resulting in an enhanced bacterial infection and in the development of a more severe colonic injury. Furthermore, we demonstrate that adoptive transfer of parasite-primed IL-10-deficient DCs fails to result in the development of a significantly enhanced C. rodentium-mediated colitis. Similarly, when the DC IL-10 response was neutralized by anti-IL-10 mAb treatment in mice that received parasite-primed DC, no deleterious effect of the parasite-primed DC on the host intestinal response to C. rodentium was detected. Thus, our results provide evidence to indicate that the H. polygyrus-dependent modulation of the host response to concurrent C. rodentium infection involves IL-10-producing DCs.
Chen
Chien-Chang
CC
Chang Gung Children's Hospital and Chang Gung University, Taoyuan, Taiwan.
Louie
Steve
S
McCormick
Beth A
BA
Walker
W Allan
WA
Shi
Hai Ning
HN
D019264:Adoptive Transfer; D000818:Animals; D018845:CD11 Antigens / Q000276:immunology / Q000378:metabolism; D044082:Citrobacter rodentium; D003092:Colitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D017206:Strongylida Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology
D018845:CD11 Antigens; D016753:Interleukin-10