Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV.
Tuberculosis (TB) contributes to the progression of HIV disease but, so far, the mechanism involved is not clear. Several cytokines accumulating in vivo at the site of mycobacterial infection up-regulate HIV expression in vitro. In this study, we assessed the role of pleural fluids recovered from seronegative patients with TB on HIV replication in acutely infected blast cells. Pleural fluids from subjects with congestive heart failure served as controls. In all cases, TB pleural fluids stimulated HIV replication in vitro. TNF-alpha, IL-6, IFN-gamma, and granulocyte/macrophage (GM)-CSF, as well as very low levels of IL-2, were detected in TB pleural fluids. An anti-IL-2 Ab preincubated with TB pleural fluids exhibited no blocking effect on HIV replication similarly to anti-IFN-gamma and anti-GM-CSF Abs. In contrast, anti-TNF-alpha and anti-IL-6 Abs decreased HIV replication by 60 and 90%, respectively. Recombinant TNF-alpha and IL-6 stimulated HIV replication, while IFN-gamma and GM-CSF had a more ambiguous role. The capacity of pleural fluids to stimulate HIV replication was specific for TB, since the capacity of control fluids was significantly lower. Finally, in contrast to PBL, which require in vitro activation for their productive infection by HIV, unstimulated tuberculous pleural lymphocytes were productively infectable by HIV. Taken together, our data suggest that the microenvironment generated by TB might increase the HIV burden in infected subjects, partly through cytokines other than IL-2, namely TNF-alpha and IL-6.
Garrait
V
V
Laboratoire d'Immunologie Pulmonaire, Hôpital Laënnec, Paris, France.
Cadranel
J
J
Esvant
H
H
Herry
I
I
Morinet
P
P
Mayaud
C
C
Israël-Biet
D
D
D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D014376:Tuberculosis / Q000276:immunology* / Q000503:physiopathology; D014779:Virus Replication / Q000502:physiology*
D016207:Cytokines