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* Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016;
Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143;
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Disease, Tokyo, Japan;
Department of Microbiology and Immunology, Division of Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
¶ Department of Pathology and
|| Department of Microbiology, New York University School of Medicine, New York, NY 10016
Mycobacterium tuberculosis (Mtb) is thought to reside in macrophages, although infected dendritic cells (DCs) have been observed. Thus, although cellular associations have been made, global characterization of the cells harboring Mtb is lacking. We have performed temporal and quantitative characterization of the cells harboring Mtb following aerosol infection of mice by using GFP-expressing bacteria and flow cytometry. We discovered that Mtb infects phagocytic cells of diverse phenotypes, that the predominant infected cell populations change with time, and that myeloid DCs are the major cell population infected with Mtb in the lungs and lymph nodes. We also found that the bacteria in the lung-draining lymph node are transported there from the lungs by a CCL19/21-dependent mechanism and that the transport of bacteria to the lymph node is a transient phenomenon despite chronic infection. In addition, we found that the lymph node cell subsets that are most efficacious in stimulating Mtb-specific, TCR-transgenic CD4+ T lymphocytes are not infected with the bacteria and are scarce or absent from the lungs of infected mice. Finally, we found that the lung cell populations that are infected with Mtb at high frequency are relatively ineffective at stimulating Ag-specific CD4+ T lymphocytes, and we have obtained evidence that live Mtb can inhibit MHC class II Ag presentation without a decrease in the surface expression of MHC class II. These results indicate that Mtb targets DC migration and Ag presentation in vivo to promote persistent infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant R01-AI051242 and by Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, Japan: Strategic Cooperation to Control Emerging and Reemerging Infections.
2 Address correspondence and reprint requests to Dr. Joel D. Ernst, Division of Infectious Diseases, New York University School of Medicine, Smilow Research Center, Room 901, 550 First Avenue, New York, NY 10016; E-mail address: joel.ernst{at}med.nyu.edu or Dr. Kiyoshi Takatsu, Department of Microbiology and Immunology, Division of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, Japan; E-mail address: takatsuk{at}ims.u-tokyo.ac.jp
3 Abbreviations used in this paper: Mtb, Mycobacterium tuberculosis; ADC, albumin dextrose catalase; 
-gal, -galactosidase; DC, dendritic cell; Tg, transgenic.
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