HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10

Tomlinson, G.S., Bell, L.C.K., Walker, N.F., Tsang, J., Brown, J.S., Breen, R., Lipman, M., Katz, D.R., Miller, R.F., Chain, B.M., Elkington, P.T. and Noursadeghi, M. (2014) HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10. The Journal of Infectious Diseases, 209 (7), 1055-1065. (doi:10.1093/infdis/jit621).

Abstract

Human immunodeficiency virus (HIV)–1 and Mycobacterium tuberculosis (Mtb) both target macrophages, which are key cells in inflammatory responses and their resolution. Therefore, we tested the hypothesis that HIV-1 may modulate macrophage responses to coinfection with Mtb. HIV-1 caused exaggerated proinflammatory responses to Mtb that supported enhanced virus replication, and were associated with deficient stimulus-specific induction of anti-inflammatory interleukin (IL)–10 and attenuation of mitogen-activated kinase signaling downstream of Toll-like receptor 2 and dectin-1 stimulation. Our in vitro data were mirrored by lower IL-10 and higher proinflammatory IL-1? in airway samples from HIV-1–infected patients with pulmonary tuberculosis compared with those with non-tuberculous respiratory tract infections. Single-round infection of macrophages with HIV-1 was sufficient to attenuate IL-10 responses, and antiretroviral treatment of replicative virus did not affect this phenotype. We propose that deficient homeostatic IL-10 responses may contribute to the immunopathogenesis of active tuberculosis and propagation of virus infection in HIV-1/Mtb coinfection.

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Contributors

Author: P.T. Elkington

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