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

Miriam Samstein,Heidi A Schreiber,Eric G Pamer,Ingrid M Leiner,Michael S Glickman,Bože Sušac

doi:10.7554/elife.01086

Miriam Samstein, Heidi A Schreiber + Show 4 more

Open Access

https://doi.org/10.7554/elife.01086

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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.

Highlights

Inflammatory monocytes (IMs) express Ly6c, CD11b and CCR2, a chemokine receptor that facilitates emigration of IMs from the bone marrow (Serbina and Pamer, 2006)
Administration of DT to these mice depletes inflammatory monocytes from the lung and mLN (Figure 1—figure supplement 1)
Immunology | Microbiology and infectious disease eLife digest Tuberculosis is a disease that kills more than one million people every year

Summary

Introduction

Inflammatory monocytes (IMs) express Ly6c, CD11b and CCR2, a chemokine receptor that facilitates emigration of IMs from the bone marrow (Serbina and Pamer, 2006). Samstein et al demonstrate that the inflammatory monocytes carry M. tuberculosis from the lungs of infected mice to the draining lymph nodes during the second week of infection. Depletion of CCR2-expressing cells 7, 9 and 11 days following infection resulted in a threefold increase in the number of live Mtb in the lungs on day 15 (Figure 1B).

Results

Conclusion