Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing MHC-II molecules capable of antigen presentation

Class II MHC (MHC-II) molecules are released by murine macrophages upon LPS stimulation and ATP signaling through the P2X7 receptor. These studies show that infection of macrophages with Mycobacterium tuberculosis (Mtb) or M. bovis strain BCG enhances MHC-II release in synergy with ATP. Shed MHC-II was contained in two distinct organelles, exosomes and plasma membrane-derived microvesicles, which were both able to present exogenous antigenic peptide to T hybridoma cells. Furthermore, microvesicles from mycobacteria-infected macrophages were able to directly present Mtb Ag 85B(241-256):I-A^b complexes that were generated by processing of Mtb Ag 85B in infected cells to both Mtb-specific T hybridoma cells and naïve P25 Mtb T cell receptor (TCR)-transgenic T cells. In the presence of pre-fixed macrophages, exosomes from mycobacterium-infected macrophages provided weak stimulation to Mtb-specific T hybridoma cells but not naïve P25 T cells. Thus, infection with Mtb primes macrophages for increased release of exosomes and microvesicles bearing Mtb peptide:MHC-II complexes that may generate anti-microbial T cell responses.

doi:10.1128/IAI.01089-09