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

Academic Article


  • Human immunodeficiency virus (HIV)-1 and Mycobacterium tuberculosis (M. tuberculosis) 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 M. tuberculosis. HIV-1 caused exaggerated proinflammatory responses to M. tuberculosis 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-1β 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/M. tuberculosis coinfection. © The Author 2013.
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    Digital Object Identifier (doi)

    Author List

  • Tomlinson GS; Bell LCK; Walker NF; Tsang J; Brown JS; Breen R; Lipman M; Katz DR; Miller RF; Chain BM
  • Start Page

  • 1055
  • End Page

  • 1065
  • Volume

  • 209
  • Issue

  • 7