Pepro Tech
Originally published online as doi:10.1189/jlb.0908574 on April 21, 2009

Published online before print April 21, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Buy
Right arrow All Versions of this Article:
jlb.0908574v1
86/1/53    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Patel, N. R.
Right arrow Articles by Koziel, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patel, N. R.
Right arrow Articles by Koziel, H.
Related Collections
Right arrowRelated Article
(Journal of Leukocyte Biology. 2009;86:53-60.)
© 2009 Society for Leukocyte Biology

Impaired M. tuberculosis-mediated apoptosis in alveolar macrophages from HIV+ persons: potential role of IL-10 and BCL-3

Naimish R. Patel1, Katharine Swan, Xin Li, Souvenir D. Tachado and Henry Koziel

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

1. Correspondence: Pulmonary, Critical Care and Sleep Medicine, BIDMC, Kirstein Hall, Room KSB-23, 330 Brookline Ave., Boston, MA 02215, USA. E-mail: npatel{at}bidmc.harvard.edu

ABSTRACT

The mechanism of increased MTb disease susceptibility in HIV+ persons remains poorly understood. Apoptosis of macrophages in response to MTb represents a critical host defense response, and decreased apoptosis may represent a mechanism of increased susceptibility to MTb in HIV. In the current study, MTb-mediated apoptosis of human AM was reduced in HIV+ subjects compared with healthy subjects in a TNF-{alpha}-dependent manner. IL-10 levels in BALF from HIV+ persons were significantly elevated compared with HIV– persons, and exogenous IL-10 reduced MTb-mediated apoptosis in healthy AM, suggesting that IL-10 could mediate decreased apoptosis observed in HIV. Further study showed that IL-10 reduced TNF release in response to MTb in AM through a reduction in TNF mRNA levels, and exogenous TNF could partially reverse IL-10-associated effects on AM apoptosis. IL-10 did not influence p-IRAK, I{kappa}B degradation, or NF-{kappa}B p65 nuclear translocation in response to MTb, but IL-10 did increase levels of AM BCL-3, an inhibitor of NF-{kappa}B nuclear activity. BCL-3 knockdown in human macrophages increased MTb-mediated TNF release. Importantly, BCL-3 levels in AM from HIV+ subjects were higher compared with healthy subjects. Taken together, these data suggest that elevated lung levels of IL-10 may impair MTb-mediated AM apoptosis in HIV through a BCL-3-dependent mechanism. BCL-3 may represent a potential therapeutic target to treat or prevent MTb disease in HIV+ persons.

Key Words: Toll-like receptors • molecules • transcription factors • NF-{kappa}B


Related Article

Editorial: Live or let die—does HIV exacerbate tuberculosis by attenuating M. tuberculosis-induced apoptosis?
Ajit Lalvani and Suzanne Hingley-Wilson
J. Leukoc. Biol. 2009 86: 9-11. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
A. Lalvani and S. Hingley-Wilson
Editorial: Live or let die--does HIV exacerbate tuberculosis by attenuating M. tuberculosis-induced apoptosis?
J. Leukoc. Biol., July 1, 2009; 86(1): 9 - 11.
[Full Text] [PDF]