Enteropathogenic Escherichia coli inhibits phagocytosis

Enteropathogenic Escherichia coli (EPEC) interacts with intestinal epitheli al cells, activating host signaling pathways leading to cytoskeletal rearra ngements and ultimately diarrhea, In this study, we demonstrate that EPEC i nteracts with the macrophage-like cell line J774A.1 to inhibit phagocytosis by these cells. Antiphagocytic activity was also observed in cultured RAW macrophage-like cells upon EPEC infection. The EPEC antiphagocytic phenotyp e was dependent on the type III secretion pathway of EPEC and its secreted proteins, including EspA, EspB, and EspD. Intimin and Tir mutants displayed intermediate antiphagocytic activity, suggesting that intimate attachment mediated by intimin-Tir binding may also play a role in antiphagocytosis. T yrosine dephosphorylation of several host proteins was observed following i nfection with secretion-competent EPEC but not with secretion-deficient mut ants. Dephosphorylation was detectable 120 min after infection with EPEC, d irectly correlating with the onset of the antiphagocytic phenotype. Inhibit ion of protein tyrosine phosphatases by pervanadate treatment increased the number of intracellular mild-type EPEC organisms to levels seen with secre tion-deficient mutants, suggesting that dephosphorylation events are linked to the antiphagocytic phenotype. No tyrosine phosphatase activity was dete cted with the EPEC-secreted proteins, suggesting that EPEC induces antiphag ocytosis via a different mechanism than Yersinia species. Taken together, t he present findings demonstrate a novel function for EPEC-secreted proteins in triggering macrophage protein tyrosine dephosphorylation and inhibition of phagocytosis.