Diminished HIV Infection of Target CD4+ T Cells in a Toll-Like Receptor 4 Stimulated in vitro Model

Frontiers in Immunology

卷:10

Ross Cromarty²  Salim S. Abdool Karim³  Lyle R. McKinnon⁴  Lenine J. P. Liebenberg⁵  Derseree Archary⁵  Alex Sigal⁶  Jo-Ann S. Passmore⁸ 

[1] Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa;

[2] Centre for the AIDS Programme of Research in South Africa, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa;

[3] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States;

[4] Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada;

[5] Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa;

[6] Max Planck Institute for Infection Biology, Berlin, Germany;

[7] Medical School, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa;

[8] National Health Laboratory Service, Cape Town, South Africa;

关键词: Toll-like receptors;    inflammation;    immune activation;    HIV;    cytokines;    innate antiviral immunity;   

DOI  :  10.3389/fimmu.2019.01705

来源: DOAJ

【 摘 要 】

Genital inflammation is associated with increased HIV acquisition risk. Induction of an inflammatory response can occur through the recognition of pathogenic or commensal microbes by Toll-like receptors (TLRs) on various immune cells. We used a in vitro peripheral blood mononuclear cell (PBMC) system to understand the contribution of TLR stimulation in inducing inflammation and the activation of target T cells, and its effect on HIV susceptibility. PBMCs were stimulated with TLR agonists LPS (TLR4), R848 (TLR7/8), and Pam3CSK4 (TLR1/2), and then infected with HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines in cell culture supernatants. Flow cytometry was used to measure the activation state (CD38 and HLA-DR), and CCR5 expression on CD4+ and CD8+ T cells. Although TLR agonists induced higher cytokine and chemokine secretion, they did not significantly activate CD4+ and CD8+ T cells and showed decreased CCR5 expression relative to the unstimulated control. Despite several classes of inflammatory cytokines and chemokines being upregulated by TLR agonists, CD4+ T cells were significantly less infectable by HIV after TLR4-stimulation than the unstimulated control. These data demonstrate that the inflammatory effects that occur in the presence TLR agonist stimulations do not necessarily translate to the activation of T cells. Most importantly, the finding that TLR4-stimulation reduces rather than increases susceptibility of CD4+ T cells to HIV infection in this in vitro system strongly suggests that the increased chemokine and possible antiviral factor expression induced by these TLR agonists play a powerful although complex role in determining HIV infection risk.

【 授权许可】

Unknown