Infection of Human Monocytes withMycobacterium tuberculosisEnhances Human Immunodeficiency Virus Type 1 Replication and Transmission to T Cells

Abstract

Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) are virulent intracellular pathogens that invade and multiply within macrophages. The effect of M. tuberculosis on HIV-1 infection and replication was analyzed in vitro using human monocyte-derived macrophages (MDM) isolated from peripheral blood mononuclear cells by countercurrent centrifugal elutriation. Preinfection of MDM with M. tuberculosis followed by HIV-1 infection resulted in an increase in p24 release, reverse transcriptase activity, and infective virus production. In contrast, no increase in HIV-1 production was observed when MDM were infected with Mycobacterium avium complex or heat-killed M. tuberculosis. Coinfected MDM were potent stimulators of T cell proliferation, while HIV-1-infected MDM failed to present exogenous tuberculin to T cells. Furthermore, coinfected MDM showed an increased capacity to transmit HIV-1 to activated T cells. These results suggest that M. tuberculosis infection can both up-regulate HIV-1 infection and replication within MDM and increase the efficiency of virus transmission from infected MDM to T cells.

Differentiation of Monocytes to Macrophages Switches theMycobacterium tuberculosisEffect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein β Expression

“…Similar to monocytic THP-1 cells, primary adherent blood monocytes increase HIV-1 replication after infection with M. tuberculosis (7,11). We previously observed that M. tuberculosis suppresses HIV-1 replication in THP-1 cells differentiated to a macrophage-like state by treatment with PMA (15).…”

“…Mutation of the C/EBP sites in the LTR produces a virus that continues to replicate in lymphocytes, but is no longer able to replicate in macrophages (21). Monocytic THP-1 cells and primary monocytes are able to up-regulate HIV-1 replication after infection with M. tuberculosis or stimulation with LPS (11,22). The enhancing effects of proinflammatory stimuli require intact C/EBP and NF-B sites in the HIV-1 LTR (6, 7).…”

“…This is in part due to NF-B activation and in part due to stimulation by the C/EBP family of transcription factors, which binds to the LTR near the NF-B sites. The enhancement of HIV-1 replication also occurs in primary blood monocytes after infection with M. tuberculosis or stimulation with mycobacterial products (11,12). Surprisingly, when monocytes are differentiated to macrophages, TNF-␣, LPS, and infection with M. tuberculosis suppress viral replication and LTR function (13)(14)(15).…”

Viable Mycobacterium avium is required for the majority of human immunodeficiency virus-induced upregulation in monocytoid cells

“…Other studies, while reporting an enhancement of HIV p24/RT levels accompanied by cytokine secretion or cytokine-mediated NF-kB-dependent transcriptional activation, did not demonstrate fully a link between these events (Zhang et al, 1995;Goletti et al, 1996Goletti et al, , 1998Vanham et al, 1996). Mancino et al (1997) have reported that viable but not heat-killed M. tuberculosis mediated an increase in HIV production in monocyte-derived macrophages, while Dezzutti et al (1999) have shown that heat-killed and viable MAC enhanced the replication of lymphocytotropic HIV-1 strain LAI in CD8-depleted PBMCs to comparable levels. They have shown further that matrix metalloproteinases are involved in in vitro M. aviuminduced HIV-1 replication in CD8-depleted PBMCs, which are mainly independent of cytokine secretion (Dezzutti et al, 1999).…”

Insertion of Host-Derived Costimulatory Molecules CD80 (B7.1) and CD86 (B7.2) into Human Immunodeficiency Virus Type 1 Affects the Virus Life Cycle

“…During the normal immune response, macrophages serve as APCs to present foreign antigens to CD4-expressing T lymphocytes. Intimate contact between an APC and a T cell leads to the upregulation of costimulatory molecules (e.g., CD80/CD86 on macrophages and CTLA-4 and CD40L on T cells) as well as the activation of HIV-1 transcription and production (35,38,50,51). Thus, it can be proposed that antigen presentation and/or the presence of some specific cytokines in the milieu surrounding HIV-1-infected macrophages will result in the expression of CD80 and CD86 and also in the production of HIV-1 particles bearing CD80 and CD86 in their envelopes.…”