Role for Rab11a in mediating TLR dependent cross-presentation responses (106.17)

• Published in: The Journal of immunology (1950) 2012-05, Vol.188 (1_Supplement), p.106-106.17
• Main Authors: Nair, Priyanka, Florey, Oliver, Baccarini, Alessia, Overholtzer, Michael, Brown, Brian, Blander, J.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.106.17

Toll-like receptor (TLR) signaling is critical for accelerated phagosome maturation and enhanced major histocompatibility complex class II (MHC II) presentation of phagocytosed antigens. Since cross-presentation is another consequence of phagosome maturation, we hypothesized that like MHC II presentation, the presentation of exogenous antigens on MHC class I (MHC I) by dendritic cells (DCs) is positively regulated by TLRs. Using antigen derived from bacteria, infected apoptotic cells or antigen-coated beads conjugated to a TLR ligand, our results show that cross-presentation is severely impaired when TLR signaling is abrogated in the cross-presenting DC or when TLR ligands are absent from phagocytic cargo. To delineate the mechanisms behind TLR enhancement of cross-presentation, we studied trafficking of MHC I in the presence or absence of TLR signaling. We observed recruitment of MHC I selectively to phagosomes containing TLR ligands along with the concomitant enrichment of the small guanosine tri-phosphatase (GTPase) Rab11a. In fact, Rab11a was crucial for TLR mediated enhancement of cross-presentation as selective knock-down of Rab11a abrogated the ability of DCs to cross-present antigen. Our results demonstrate a role for Rab11a in trafficking MHC I to phagosomes that engage TLR signaling, thus mediating enhanced cross-presentation of microbial antigens. Results from our studies have implications on anti-viral and anti-bacterial immunity as well as tumor immunotherapy.