Essential yet limited role for CCR2+ inflammatory monocytes during Mycobacterium tuberculosis--specific T cell priming

Defense against infection by Mycobacterium tuberculosis (Mtb), an inhaled pathogen that causes over 1.5 million deaths per year, is mediated by CD4 T cells. CCR2+ inflammatory monocytes (IMs) have been implicated in Mtb-specific CD4 T cell responses but their in vivo contribution remains unresolved. IMs traffic to and from sites of inflammation, differentiate into monocyte derived dendritic cells and can induce antigen-specific T cell proliferation. Herein we show that transient ablation of IMs during infection prevents Mtb delivery to pulmonary lymph nodes, thereby reducing CD4 T cell responses and Mtb clearance. Transfer of MHC class II-expressing IMs to MHC class II-deficient, monocyte depleted recipients, while restoring Mtb transport to mLNs, does not enable Mtb-specific CD4 T cell priming. On the other hand, transfer of MHC class II-deficient IMs fully corrects CD4 T cell priming in monocyte-depleted, MHC class II-expressing mice. Specific depletion of classical DC does not reduce Mtb delivery to pulmonary lymph nodes but markedly reduces CD4 T cell priming. Thus, although IMs acquire characteristics of DCs during infection while delivering Mtb to lymph nodes, classical DCs but not monocyte-derived DCs induce proliferation of Mtb-specific CD4 T cells.