title: Coinfection with an intestinal helminth impairs host innate immunity against Salmonella enterica serovar Typhimurium and exacerbates intestinal inflammation in mice.
abstract: Salmonella enterica serovar Typhimurium is a Gram-negative food-borne pathogen that is a major cause of acute gastroenteritis in humans. The ability of the host to control such bacterial pathogens may be influenced by host immune status and by concurrent infections. Helminth parasites are of particular interest in this context because of their ability to modulate host immune responses and because their geographic distribution coincides with those parts of the world where infectious gastroenteritis is most problematic. To test the hypothesis that helminth infection may negatively regulate host mucosal innate immunity against bacterial enteropathogens, a murine coinfection model was established by using the intestinal nematode Heligmosomoides polygyrus and S. Typhimurium. We found that mice coinfected with S. Typhimurium and H. polygyrus developed more severe intestinal inflammation than animals infected with S. Typhimurium alone. The enhanced susceptibility to Salmonella-induced intestinal injury in coinfected mice was found to be associated with diminished neutrophil recruitment to the site of bacterial infection that correlated with decreased expression of the chemoattractants CXCL2/macrophage inflammatory protein 2 (MIP-2) and CXCL1/keratinocyte-derived chemokine (KC), poor control of bacterial replication, and exacerbated intestinal inflammation. The mechanism of helminth-induced inhibition of MIP-2 and KC expression involved interleukin-10 (IL-10) and, to a lesser extent, IL-4 and IL-13. Ly6G antibody-mediated depletion of neutrophils reproduced the adverse effects of H. polygyrus on Salmonella infection. Our results suggest that impaired neutrophil recruitment is an important contributor to the enhanced severity of Salmonella enterocolitis associated with helminth coinfection.
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA College of Veterinary Medicine, Jilin University, Jilin, China.
authors: Libo
authors: L
authors: Su
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Chien-wen
authors: CW
authors: Su
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Yujuan
authors: Y
authors: Qi
authors: Jilin Agricultural University, Jilin, China.
authors: Guilian
authors: G
authors: Yang
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Mei
authors: M
authors: Zhang
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Bobby J
authors: BJ
authors: Cherayil
authors: College of Veterinary Medicine, Jilin University, Jilin, China.
authors: Xichen
authors: X
authors: Zhang
authors: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA shiha@helix.mgh.harvard.edu.
authors: Hai Ning
authors: HN
authors: Shi
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D007378:Interleukins / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology / Q000382:microbiology
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D007378:Interleukins