Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens

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. © 2014 su et al.