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Resistance of HIV-infected macrophages to CD8+ T lymphocyte-mediated killing drives activation of the immune system.


ABSTRACT: CD4+ T lymphocytes are the principal target of human immunodeficiency virus (HIV), but infected macrophages also contribute to viral pathogenesis. The killing of infected cells by CD8+ cytotoxic T lymphocytes (CTLs) leads to control of viral replication. Here we found that the killing of macrophages by CTLs was impaired relative to the killing of CD4+ T cells by CTLs, and this resulted in inefficient suppression of HIV. The killing of macrophages depended on caspase-3 and granzyme B, whereas the rapid killing of CD4+ T cells was caspase independent and did not require granzyme B. Moreover, the impaired killing of macrophages was associated with prolonged effector cell-target cell contact time and higher expression of interferon-? by CTLs, which induced macrophage production of pro-inflammatory chemokines that recruited monocytes and T cells. Similar results were obtained when macrophages presented other viral antigens, suggestive of a general mechanism for macrophage persistence as antigen-presenting cells that enhance inflammation and adaptive immunity. Inefficient killing of macrophages by CTLs might contribute to chronic inflammation, a hallmark of chronic disease caused by HIV.

SUBMITTER: Clayton KL 

PROVIDER: S-EPMC6025741 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Resistance of HIV-infected macrophages to CD8<sup>+</sup> T lymphocyte-mediated killing drives activation of the immune system.

Clayton Kiera L KL   Collins David R DR   Lengieza Josh J   Ghebremichael Musie M   Dotiwala Farokh F   Lieberman Judy J   Walker Bruce D BD  

Nature immunology 20180418 5


CD4<sup>+</sup> T lymphocytes are the principal target of human immunodeficiency virus (HIV), but infected macrophages also contribute to viral pathogenesis. The killing of infected cells by CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs) leads to control of viral replication. Here we found that the killing of macrophages by CTLs was impaired relative to the killing of CD4<sup>+</sup> T cells by CTLs, and this resulted in inefficient suppression of HIV. The killing of macrophages depended on casp  ...[more]

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