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Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.


ABSTRACT: Innate lymphoid cells (ILCs) are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity. Highly active antiretroviral (HAART) therapy in HIV-1 patients efficiently rescued the ILC1 numbers and reduced their activation, but failed to restore their functionality. We also found that blocking type-I interferon (IFN-I) signaling during HIV-1 infection in vivo in humanized mice prevented HIV-1 induced depletion or apoptosis of ILC1 cells. Therefore, we have identified the CD4+ ILC1 cells as a new target population for HIV-1 infection, and revealed that IFN-I contributes to the depletion of ILC1s during HIV-1 infection.

SUBMITTER: Zhao J 

PROVIDER: S-EPMC5773236 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.

Zhao Juanjuan J   Cheng Liang L   Wang Hongbo H   Yu Haisheng H   Tu Bo B   Fu Qiang Q   Li Guangming G   Wang Qi Q   Sun Yanling Y   Zhang Xin X   Liu Zhenwen Z   Chen Weiwei W   Zhang Liguo L   Su Lishan L   Zhang Zheng Z  

PLoS pathogens 20180105 1


Innate lymphoid cells (ILCs) are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired the  ...[more]

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