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

Elife. 2013 Nov 12:2:e01086. doi: 10.7554/eLife.01086.

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.

Keywords: CD 4 T cell priming; Mycobacterium tuberculosis; dendritic cell; inflammatory monocyte.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Inflammation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CCR2 / physiology*
  • T-Lymphocytes / immunology*

Substances

  • Ccr2 protein, mouse
  • Receptors, CCR2