TLR7 enhances cross-presentation in Ly6C(+) monocytes by targeting endosomal properties.

Abstract

Abstract Effector functions of monocytes beyond terminal differentiation has recently come to light. In the present study we have made the novel discovery that Ly6C(+) monocytes can acquire cell-associated Ag from apoptotic cells, termed as efferocytosis. This property was enhanced by the presence of pathogenic stimuli (TLR ligands) directly acting on monocytes. Furthermore, we have shown that monocytes can cross-present Ag acquired from those apoptotic cells, with differential ability of TLR4 and TLR7 ligands in enhancing that process. This has led us to investigate the role of various pathogenic stimuli beyond these two ligands. Our data has confirmed our previous findings and further established the fact that among known TLR ligands, TLR7 selectively enhanced the presentation of peptides on MHC-I molecules. To elucidate the mechanism, we performed RNA sequencing on monocytes treated with a TLR7 ligand showing the involvement of endosomal proteins in antigen presentation, specifically subunits of the NADPH oxidase. Our data clearly demonstrated the role of Ncf-1 in TLR7 mediated enhanced activation of antigen specific CD8+ T cells. Overall, this study defines a unique role for Ly6C(+) monocytes in promoting immunity against single-stranded virus by regulating endosomal pH, a characterized process required for Batf3-dependent DC cross-presentation.