Essential yet limited role for CCR2+ inflammatory monocytes during Mycobacterium tuberculosis-specific T cell priming
Miriam Samstein,
Heidi A Schreiber,
Ingrid M Leiner,
Bože Sušac,
Michael S Glickman,
Eric G Pamer
Affiliations
Miriam Samstein
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States; Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States; Weill Cornell, Rockefeller, Sloan-Kettering Tri-Institutional MD-PhD Program, New York, United States
Heidi A Schreiber
Laboratory of Molecular Immunology, The Rockefeller University, New York, United States
Ingrid M Leiner
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States
Bože Sušac
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States
Michael S Glickman
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States; Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States
Eric G Pamer
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, United States; Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States
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.
