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

Abstract

Defense against infection by Mycobacterium tuberculosis (Mtb) 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. Herein, we show that transient ablation of IMs during infection prevents Mtb delivery to pulmonary lymph nodes, reducing CD4 T cell responses. 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 corrects CD4 T cell priming in monocyte-depleted, MHC class II-expressing mice. Specific depletion of classical DCs does not reduce Mtb delivery to pulmonary lymph nodes but markedly reduces CD4 T cell priming. Thus, although IMs acquire characteristics of DCs while delivering Mtb to lymph nodes, cDCs but not moDCs induce proliferation of Mtb-specific CD4 T cells.DOI: http://dx.doi.org/10.7554/eLife.01086.001

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