title: Immune Responses of HIV-1 Tat Transgenic Mice to Mycobacterium Tuberculosis W-Beijing SA161.
abstract: BACKGROUND
  Mycobacterium tuberculosis remains among the leading causes of death from an infectious agent in the world and exacerbates disease caused by the human immunodeficiency virus (HIV). HIV infected individuals are prone to lung infections by a variety of microbial pathogens, including M. tuberculosis. While the destruction of the adaptive immune response by HIV is well understood, the actual pathogenesis of tuberculosis in co-infected individuals remains unclear. Tat is an HIV protein essential for efficient viral gene transcription, is secreted from infected cells, and is known to influence a variety of host inflammatory responses. We hypothesize Tat contributes to pathophysiological changes in the lung microenvironment, resulting in impaired host immune responses to infection by M. tuberculosis.
  
  
  RESULTS
  Herein, we show transgenic mice that express Tat by lung alveolar cells are more susceptible than non-transgenic control littermates to a low-dose aerosol infection of M. tuberculosis W-Beijing SA161. Survival assays demonstrate accelerated mortality rates of the Tat transgenic mice compared to non-transgenics. Tat transgenic mice also showed poorly organized lung granulomata-like lesions. Analysis of the host immune response using quantitative RT-PCR, flow cytometry for surface markers, and intracellular cytokine staining showed increased expression of pro-inflammatory cytokines in the lungs, increased numbers of cells expressing ICAM1, increased numbers of CD4+CD25+Foxp3+ T regulatory cells, and IL-4 producing CD4+ T cells in the Tat transgenics compared to infected non-tg mice.
  
  
  CONCLUSIONS
  Our data show quantitative differences in the inflammatory response to the SA161 clinical isolate of M. tuberculosis W-Beijing between Tat transgenic and non-transgenic mice, suggesting Tat contributes to the pathogenesis of tuberculosis.
authors: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, 80045, USA.
authors: Jennifer R
authors: JR
authors: Honda
authors: Shaobin
authors: S
authors: Shang
authors: Crystal A
authors: CA
authors: Shanley
authors: Megan L
authors: ML
authors: Caraway
authors: Marcela
authors: M
authors: Henao-Tamayo
authors: Edward D
authors: ED
authors: Chan
authors: Randall J
authors: RJ
authors: Basaraba
authors: Ian M
authors: IM
authors: Orme
authors: Diane J
authors: DJ
authors: Ordway
authors: Sonia C
authors: SC
authors: Flores