Essential yet limited role for CCR2⁺ inflammatory monocytes during Mycobacterium tuberculosis-specific T cell priming.
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.
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States.
Miriam
M
Samstein
Heidi A
HA
Schreiber
Ingrid M
IM
Leiner
Boze
B
Susac
Michael S
MS
Glickman
Eric G
EG
Pamer
D000818:Animals; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054390:Receptors, CCR2 / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2
CD 4 T cell priming; Mycobacterium tuberculosis; dendritic cell; inflammatory monocyte