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Infection and Immunity, March 2001, p. 1433-1439, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1433-1439.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Mycobacterium smegmatis-Induced Cytokine Production by Human Macrophages In Vitro

Frank A. Post,1,2,dagger Claudia Manca,2 Olivier Neyrolles,3 Bernhard Ryffel,1 Douglas B. Young,3 and Gilla Kaplan2,*

Department of Immunology, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa1; Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 100212; and Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, London W2 1PG, United Kingdom3

Received 19 October 2000/Returned for modification 15 November 2000/Accepted 27 November 2000

Vaccination of mice with Mycobacterium vaccae or M. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis, expressed in M. vaccae or M. smegmatis (M. smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-alpha ) (P < 0.01), interleukin-12 (IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05), compared to infection with M. smegmatis vector (M. smegV). Infection with M. smeg19kDa and with M. smegV had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected with M. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated (M. smeg19NOG), nonsecreted (M. smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced production of TNF-alpha or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-alpha and IL-12 production, possibly leading to reduced induction of T-cell activation.

* Corresponding author. Mailing address: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8375. Fax: (212) 327-8875. E-mail: kaplang{at}rockvax.rockefeller.edu.

dagger Present address: Infectious Diseases Clinical Research Unit, The Lung Institute, University of Cape Town, Cape Town, South Africa.

Infection and Immunity, March 2001, p. 1433-1439, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1433-1439.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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