Increased Mycobacterium tuberculosis growth in HIV-1-infected human macrophages: role of tumour necrosis factor-alpha.
Synergism between Mycobacterium tuberculosis (M. tuberculosis) and HIV-1 infections was demonstrated in several in vitro models and clinical studies. Here, we investigated their reciprocal effects on growth in chronically HIV-1-infected promonocytic U1 cells and in acutely infected monocyte-derived macrophages (MDM). Phagocytosis of M. tuberculosis induced HIV-1 expression in U1 cells, together with increased TNF-alpha production. M. tuberculosis growth, evaluated by competitive PCR, was greater in HIV-1-infected MDM compared to uninfected cells. M. tuberculosis phagocytosis induced greater TNF-alpha and IL-10 production in HIV-1-infected MDM than in uninfected cells. In uninfected MDM, addition of TNF-alpha and IFN-gamma decreased, whereas IL-10 increased M. tuberculosis growth. On the contrary, in HIV-1-infected MDM, addition of TNF-alpha and IFN-gamma increased, whereas IL-10 has no effect on M. tuberculosis growth. TNF-alpha seems to play a pivotal role in the enhanced M. tuberculosis growth observed in HIV-1-infected MDM, being unable to exert its physiological antimycobacterial activity. Here, for the first time we demonstrated an enhanced M. tuberculosis growth in HIV-1-infected MDM, in line with the observed clinical synergism between the two infections.
Imperiali
F G
FG
Division of Hematology, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy.
Zaninoni
A
A
La Maestra
L
L
Tarsia
P
P
Blasi
F
F
Barcellini
W
W
D018925:Chemokines / Q000096:biosynthesis; D015658:HIV Infections / Q000382:microbiology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology* / Q000821:virology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000494:pharmacology; D020298:U937 Cells
D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma