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HIV infection modulates IL-1β response to LPS stimulation through a TLR4-NLRP3 pathway in human liver macrophages.

Abstract：

:IL-1β is an important mediator of innate inflammatory responses and has been shown to contribute to liver injury in a number of etiologies. HIV patients have increased necroinflammation and more rapid fibrosis progression in chronic liver injury compared to non-HIV-infected patients. As the resident liver macrophage is critical to the IL-1β response to microbial translocation in chronic liver disease, we aim to examine the impact of HIV-1 and LPS stimulation on the IL-1β response of the resident hepatic macrophages. We isolated primary human liver macrophages from liver resection specimens, treated them with HIV-1BaL and/or LPS ex vivo, examined the IL-1β response, and then studied underlying mechanisms. Furthermore, we examined IL-1β expression in liver tissues derived from HIV-1 patients compared to those with no underlying liver disease. HIV-1 up-regulated TLR4 and CD14 expression on isolated primary CD68+ human liver macrophages and contributed to the IL-1β response to LPS stimulation as evidenced by TLR4 blocking. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) was shown to be involved in the IL-1β response of liver macrophages to HIV-1 infection and NLRP3 blocking experiments in primary CD68+ liver macrophages confirmed the contribution of the NLRP3-caspase 1 inflammatory signaling pathway in the IL-1β response. High in situ IL-1β expression was found in CD68+ cells in human liver tissues from HIV-1-infected patients, suggesting a critical role of IL-1β responses in patients infected by HIV. HIV infection sensitizes the IL-1β response of liver macrophages to LPS through up-regulation of CD14 and TLR4 expression and downstream activation of the NLRP3-caspase 1 pathway. These findings have implications for enhanced immune activation in HIV+ patients and mechanisms for rapid fibrosis progression in patients with chronic liver injury.

journal_name

J Leukoc Biol

journal_title

Journal of leukocyte biology

authors

Zhang L,Mosoian A,Schwartz ME,Florman SS,Gunasekaran G,Schiano T,Fiel MI,Jiang W,Shen Q,Branch AD,Bansal MB

doi

10.1002/JLB.4A1018-381R

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

783-795

issue

eissn

0741-5400

issn

1938-3673

journal_volume

105

pub_type

杂志文章

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HIV infection modulates IL-1β response to LPS stimulation through a TLR4-NLRP3 pathway in human liver macrophages.