Rab11a GTPase controls Toll-like receptor 4 trafficking and signaling

Abstract

Rab GTPases are involved in controlling the endosomal pathway, and we have developed an expression system allowing us to study the expression and trafficking of these molecules in live cells. Toll-like receptor 4 (TLR4) is important in our defence against Gram-negative bacteria and must be regulated to elicit a proper response to invading pathogens. We describe a novel trafficking pathway of TLR4 from the perinuclear endocytic recycling compartment (ERC) to E. coli phagosomes. We found that Rab11a was involved in transport of TLR4 vesicles to phagosomes in a process that required TLR4 signaling. Suppression of Rab11a reduced the amount of TLR4 inthe ERC and on phagosomes leading to inhibition of the IRF3 signaling pathway induced by E. coli. We propose that Rab11a is a master regulator that integrates essential events occuring when macrophages encounter Gram-negative bacteria, allowing TLR4 recruitment to the phagosome and IRF3 activation.