J. Celli et al., Enteropathogenic Escherichia coli mediates antiphagocytosis through the inhibition of PI 3-kinase-dependent pathways, EMBO J, 20(6), 2001, pp. 1245-1258
The extracellular pathogen enteropathogenic Escherichia coli (EPEC) uses a
type III secretion system to inhibit its uptake by macrophages. We show tha
t EPEC antiphagocytosis is independent of the translocated intimin receptor
Tir and occurs by preventing F-actin polymerization required for bacterial
uptake. EPEC-macrophage contact triggered activation of phosphatidylinosit
ol (PI) 3-kinase, which was subsequently inhibited in a type III secretion-
dependent manner. Inhibition of PI 3-kinase significantly reduced uptake of
a secretion-deficient mutant, without affecting antiphagocytosis by the wi
ld type, suggesting that EPEC blocks a PI 3-kinase-dependent phagocytic pat
hway. EPEC specifically inhibited Fc gamma receptor- but not CR3-receptor m
ediated phagocytosis of opsonized zymosan, We showed that EPEC inhibits PI
3-kinase activity rather than its recruitment to the site of bacterial cont
act. Phagocytosis of a secretion mutant correlated with the association of
PI 3-kinase with tyrosine-phosphorylated proteins, which wild-type EPEC pre
vented. These results show that EPEC blocks its uptake by inhibiting a PI 3
-kinase-mediated pathway, and translocates effecters other than Tir to inte
rfere with actin-driven host cell processes. This constitutes a novel mecha
nism of phagocytosis avoidance by an extracellular pathogen.