title: Development of fatal intestinal inflammation in MyD88 deficient mice co-infected with helminth and bacterial enteropathogens.
abstract: Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To determine whether and how an intestinal helminth parasite, Heligomosomoides polygyrus, might impact the TLR signaling pathway during the response to a bacterial enteropathogen, MyD88 knockout and wild-type C57BL/6 mice were infected with H. polygyrus, the bacterial enteropathogen Citrobacter rodentium, or both. We found that MyD88 knockout mice co-infected with H. polygyrus and C. rodentium developed more severe intestinal inflammation and elevated mortality compared to the wild-type mice. The enhanced susceptibility to C. rodentium, intestinal injury and mortality of the co-infected MyD88 knockout mice were found to be associated with markedly reduced intestinal phagocyte recruitment, decreased expression of the chemoattractant KC, and a significant increase in bacterial translocation. Moreover, the increase in bacterial infection and disease severity were found to be correlated with a significant downregulation of antimicrobial peptide expression in the intestinal tissue in co-infected MyD88 knockout mice. Our results suggest that the MyD88 signaling pathway plays a critical role for host defense and survival during helminth and enteric bacterial co-infection.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin, China; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Libo
authors.initials: L
authors.lastname: Su
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America; Qinghai University Medical School, Xining, Qinghai, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Meiqian
authors.initials: M
authors.lastname: Weng
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Chienwen
authors.initials: C
authors.lastname: Su
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Hai Ning
authors.initials: HN
authors.lastname: Shi
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000382:microbiology / Q000469:parasitology; D005260:Female; D006373:Helminthiasis / Q000235:genetics / Q000382:microbiology / Q000469:parasitology; D007249:Inflammation / Q000235:genetics / Q000382:microbiology / Q000469:parasitology; D007410:Intestinal Diseases / Q000235:genetics / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88