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Infection and Immunity, May 2004, p. 2628-2634, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2628-2634.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Down-Modulation of Lung Immune Responses by Interleukin-10 and Transforming Growth Factor ß (TGF-ß) and Analysis of TGF-ß Receptors I and II in Active Tuberculosis

M. Glória Bonecini-Almeida,1 John L. Ho,2* Neio Boéchat,3 Richard C. Huard,2 Sadhana Chitale,2 Howard Doo,2 Jiayuan Geng,2 Lorena Rego,3 Luiz Claudio Oliveira Lazzarini,2,3 Afrânio L. Kritski,3 Warren D. Johnson Jr.,2 Timothy A. McCaffrey,4 and José R. Lapa e Silva3*

Instituto de Pesquisas, Clinica Evandro Chagas, Serviço de Immulogia, FIOCRUZ,1 Laboratório Multidisciplinar de Pesquisa e Divisão de Pneumologia e Tisiologia, Instituto de Doenças do Tórax/Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,3 Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York,2 George Washington University Medical Center, Washington, D.C.4

Received 22 October 2003/ Returned for modification 16 December 2003/ Accepted 11 February 2004

Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor ß (TGF-ß) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-ß receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-{gamma}) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-{gamma}, and bioactive TGF-ß were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-ß, as well as coexpression of TGF-ß RI and RII (required for cellular response to TGF-ß), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis.

* Corresponding author. Mailing address for John L. Ho: Division of International Medicine & Infectious Diseases, Weill Medical College of Cornell University, 1300 York Ave., Rm. A-421, New York, NY 10021. Phone: (212) 746-6316. Fax: (212) 746-8675. E-mail: jlho{at}med.cornell.edu. Mailing address for Jose R. Lapa e Silva: Laboratório Multidisciplinar de Pesquisa, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Avenida Brigadeiro Trompovski, s/n, Ilha do Fundao, Rio de Janeiro, 21941-590, Rio de Janeiro, RJ, Brazil. Phone: 55-21-2562-2669. Fax: 55-21-2290-3520. E-mail: jrlapa.ntg{at}terra.com.br.

Editor: S. H. E. Kaufmann

Infection and Immunity, May 2004, p. 2628-2634, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2628-2634.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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