Induction of HIV type 1 expression correlates with T cell responsiveness to mycobacteria in patients coinfected with HIV type 1 and Mycobacterium tuberculosis.
An in vitro mononuclear cell system to model the microenvironment of coinfection with HIV-1 and Mycobacterium tuberculosis (MTB) was developed. This cellular system was used to assess the interaction of MTB-infected monocytes and T cells from dually infected HIV-1/TB patients with pulmonary tuberculosis (TB). Subjects with higher induction of HIV-1 gag/pol mRNA expression after MTB stimulation had increased MTB-specific T cell IFN-gamma and TNF-alpha production. Lack of HIV-1 mRNA induction did not correlate with increased induction of regulatory T cells (T-reg) as measured by MTB-induced Foxp3 mRNA. HIV-1 induction did not significantly correlate with clinical parameters including plasma HIV-1 viral load or CD4(+) T cell count. These data model MTB-induced HIV-1 replication at the microenvironment of MTB reactivation/infection. The data suggest that the magnitude of MTB-specific T cell responses drives local viral pathogenesis regardless of the stage of HIV-1 disease as reflected by plasma viral load or CD4(+) T cell count.
Canaday
David H
DH
Division of Infectious Diseases, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA. dxc44@case.edu
Wu
Mianda
M
Lu
Shigou
S
Aung
Htin
H
Peters
Pierre
P
Baseke
Joy
J
Mackay
Wilma
W
Mayanja-Kizza
Harriet
H
Toossi
Zahra
Z
D000293:Adolescent; D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma