Su, LiboQi, YujuanZhang, MeiWeng, MeiqianZhang, XichenSu, ChienwenShi, Hai2014-08-132014Su, Libo, Yujuan Qi, Mei Zhang, Meiqian Weng, Xichen Zhang, Chienwen Su, and Hai Ning Shi. 2014. “Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens.” PLoS Neglected Tropical Diseases 8 (7): e2987. doi:10.1371/journal.pntd.0002987. http://dx.doi.org/10.1371/journal.pntd.0002987.1935-2727http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717503Infections 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.en-USBiology and Life SciencesComputational BiologyPopulation ModelingInfectious Disease ModelingImmunologyMicrobiologyMedicine and Health SciencesGastroenterology and HepatologyGastrointestinal InfectionsInflammatory Bowel DiseaseInfectious DiseasesBacterial DiseasesParasitic DiseasesTropical DiseasesNeglected Tropical DiseasesJournal Article2014-08-1310.1371/journal.pntd.0002987