Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type 1.

Abstract

Blood monocytes from patients with active pulmonary tuberculosis and age-matched healthy purified protein derivative-reactive donors were infected with human immunodeficiency virus type 1 (HIV-1)JR-FL in vitro to assess their susceptibility to productive infection by HIV-1. HIV-1 p24 levels (enzyme-linked immunosorbent assay) in supernatants of infected cells from patients with tuberculosis, albeit variable, were significantly higher at days 10-20 of culture; the maximum levels of p24 antigen were greater in supernatants of HIV-1-infected monocytes from patients than maximum levels for controls (p < 0.05). The maximum increment in p24 levels for patients also exceeded that for controls (p < 0.05). Entry of HIV-1 and/or initiation of reverse transcription, measured by polymerase chain reaction using HIV-1 R/U5 primer pairs, was variable and low in infected monocytes from both patients and controls, and did not correlate with HIV-1 p24 levels. The frequency of infected cells as assessed by endpoint dilution viral cultures was similar for both groups. Therefore, blood monocytes from patients with active tuberculosis can develop a highly productive infection with HIV-1 that does not appear to be due to enhanced HIV entry or higher frequency of infected cells. The enhanced susceptibility may result directly from activation of monocytes by exposure to Mycobacterium tuberculosis and its products in situ.

HIV and Tuberculosis: a Deadly Human Syndemic

“…Early after the recognition that TB and HIV were converging to amplify the problems that each of the epidemics posed alone (231), peripheral blood monocytes from patients with active TB were found to be more susceptible to productive infection by HIV in vitro (247). Moreover, levels of HIV have been found to be higher in M. tuberculosis-infected regions of the lungs than in the uninvolved regions of the same patient (274).…”

“…The development of TB is associated with increased HIV replication, as measured by the viral load at the site of TB infection in the lungs as well as by the plasma viral load (246,247). As described in more detail below, M. tuberculosis activates HIV transcription and enhances viral entry in vitro (55).…”

Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat.

“…Mortality of dually infected HIV/tuberculosis individuals has been reported to be as high as 50% at 12 mo in New York compared to < 10% due to M. tuberculosis alone, and mortality among HIV-1-infected individuals with multidrug-resistant M. tuberculosis can be as high as 90% at 9 mo (13). Toosi et al (14) reported an enhanced susceptibility of blood monocytes from patients with tuberculosis to productive infection with Alveolar macrophages are primary players in host defense phagocytosing M. tuberculosis, and are capable of being infected by HIV-1. At sites of active M. tuberculosis infection, bacilli-laden macrophages may be HIV-infected as well.…”

Co-Infection with HIV and Mycobacterium tuberculosis: immunologic interactions, disease progression, and survival

“…Isoniazid, by its ability to kill M. tuberculosis, obviates the host immune response to contain M. tuberculosis and thereby, lessens viral burden and prolongs HIV symptom-free interval and survival. Furthermore, the immune response during active tuberculosis has been shown to prime peripheral blood cells and enhance their susceptibility for HIV infection (Tossi et al 1993).…”