The Rab11a GTPase Controls Toll-like Receptor 4-Induced Activation of Interferon Regulatory Factor-3 on Phagosomes

Toll-like receptor 4 (TLR4) is indispensable for recognition of Gram-negative bacteria We described a trafficking pathway for TLR4 from the endocytic recycling compartment (ERC) to E coli phagosomes We found a prominent colocalization between TLR4 and the small GTPase Rab11a in the ERC, and Rab11a was involved in the recruitment of TLR4 to phagosomes in a process requiring TLR4 signaling Also, Toll-receptor-associated molecule (TRAM) and interferon regulatory factor-3 (IRF3) localized to E coli phagosomes and internalization of E coli was required for a robust interleron-beta induction Suppression of Rab11a reduced TLR4 in the ERC and on phagosomes leading to inhibition of the IRF3 signaling pathway induced by E coli, whereas activation of the transcription factor NF-kappa B was unaffected Moreover, Rab11a silencing reduced the amount of TRAM on phagosomes Thus, Rab11a is an important regulator of TLR4 and TRAM transport to E coli phagosomes thereby controlling IRF3 activation from this compartment