HIV-1 Tat Upregulates TREM1 Expression in Human Microglia

Author:

Campbell Grant R.1ORCID,Rawat Pratima2,To Rachel K.2ORCID,Spector Stephen A.23ORCID

Affiliation:

1. *Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD

2. †Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, CA

3. ‡Rady Children’s Hospital, San Diego, CA

Abstract

Abstract Because microglia are a reservoir for HIV and are resistant to the cytopathic effects of HIV infection, they are a roadblock for any HIV cure strategy. We have previously identified that triggering receptor expressed on myeloid cells 1 (TREM1) plays a key role in human macrophage resistance to HIV-mediated cytopathogenesis. In this article, we show that HIV-infected human microglia express increased levels of TREM1 and are resistant to HIV-induced apoptosis. Moreover, upon genetic inhibition of TREM1, HIV-infected microglia undergo cell death in the absence of increased viral or proinflammatory cytokine expression or the targeting of uninfected cells. We also show that the expression of TREM1 is mediated by HIV Tat through a TLR4, TICAM1, PG-endoperoxide synthase 2, PGE synthase, and PGE2-dependent manner. These findings highlight the potential of TREM1 as a therapeutic target to eradicate HIV-infected microglia without inducing a proinflammatory response.

Funder

HHS | NIH | National Institute of Mental Health

HHS | NIH | National Institute of Neurological Disorders and Stroke

University of South Dakota

International Maternal Pediatric Adolescent AIDS Clinical Trials Network

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

Reference151 articles.

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