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The Interaction of Monocyte Chemoattractant Protein‐1 and Tumour Necrosis Factor‐α in Mycobacterium tuberculosis ‐induced HIV‐1 Replication at Sites of Active Tuberculosis
Author(s) -
MayanjaKizza H.,
Wu M.,
Aung H.,
Liu S.,
Luzze H.,
Hirsch C.,
Toossi Z.
Publication year - 2009
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2009.02246.x
Subject(s) - monocyte , tumor necrosis factor alpha , peripheral blood mononuclear cell , mycobacterium tuberculosis , tuberculosis , virology , biology , immunology , in vitro , medicine , pathology , biochemistry
Tuberculosis (TB) is a prominent opportunistic infection in HIV‐1‐infected subjects and enhances HIV‐1 replication. TB is associated with excess monocyte chemoattractant protein (MCP)‐1 and tumour necrosis factor (TNF)‐α activity in situ , both of which are implicated in transcriptional activation of HIV‐1. The role of MCP‐1 and TNF‐α in activation of HIV‐1 during TB and by Mycobacterium tuberculosis (MTB) in mononuclear cells from HIV‐1/TB subjects with pleural TB was examined here. Extremely high levels of MCP‐1 (as compared with TNF‐α) protein and mRNA were found in pleural fluid and pleural fluid mononuclear cells. Levels of MCP‐1 mRNA were sustained during in vitro culture of pleural fluid mononuclear cells. Neutralization of MCP‐1 (but not TNF‐α), resulted in inhibition of MTB induced HIV‐1 gag/pol mRNA. Neutralization of both MCP‐1 and TNF‐α, however, abrogated the effect of anti‐MCP‐1 antibody on HIV‐1 mRNA. LMP‐420, a small molecular transcriptional inhibitor of both TNF‐α and MCP‐1 expression, did not reduce MTB‐induced HIV‐1 expression. These data imply that MCP‐1 activity may be critical to activation of HIV‐1 at sites of TB. An interplay of MCP‐1 and TNF‐α is also suggested.