Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway.

VELÁSQUEZ L. N., MILILLO M. A., DELPINO M. V.,TROTTA A., MERCOGLIANO M. F., POZNER R. G., SCHILLACI R., ELIZALDE P. V., GIAMBARTOLOMEI G. H., BARRIONUEVO P.

IMMUNOLOGY AND CELL BIOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2017

0818-9641

Brucella abortus is able to persist inside the host despite the development ofpotent CD8+ T cell responses. We have recently reported the abilityof B. abortus to inhibit theIFN-γ-induced MHC-I cell surface expression on human monocytes. This phenomenonwas due to the B. abortus-mediated retention of MHC-I molecules withinthe Golgi apparatus and was dependent on bacterial viability. However, the implicationsof bacterial virulence or replicative capacity and the signaling pathways remainedunknown. Here, we demonstrated that the B. abortus mutant strains RB51and virB10- are able to inhibit MHC-I expression in the same manner as wild type B. abortus, even though theyare unable to persist inside human monocytes for a long period of time. Consistentwith this, the phenomenon was triggered early in time and could be observed at8 h post-infection. At 24 h and 48 h it was even stronger. Regarding thesignaling pathway, targeting EGF receptor (EGFR), ErbB2 (HER2) or inhibition ofTACE, one of the enzymes which generates soluble EGF-like ligands, resulted inpartial recovery of MHC-I surface expression. Moreover, recombinant EGF and TGF-αas well as the combination of both were also able to reproduce the B. abortus-induced MHC-I down-modulation.Finally, wheninfection was performed in the presence of an Erk1/2 inhibitor, MHC-I surfaceexpression was significantly recovered. Overall, theseresults describe how B. abortusevades CD8+ T cell responses early during infection and exploits theEGFR-ERK signaling pathway to escape from the immune system and favorchronicity.