HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1.
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy. Here, we investigated the potential role of TREM-1 in HIV latency in macrophages. Our data show that human macrophages infected with HIV show an increased expression of TREM-1. In parallel, direct exposure to the HIV-related proteins Tat or gp120 induces TREM-1 expression in macrophages and confers anti-apoptotic attributes.NF-κB p65 silencing identified that these proteins induce TREM-1 in p65-dependent manner. TREM-1 silencing in macrophages exposed to HIV-related proteins led to increased caspase 3 activation and reduced Bcl-2 expression, rendering them susceptible to apotosis. These novel data reveal that TREM-1 may play a critical role in establishing HIV reservoir in macrophages by inhibiting apoptosis. Therefore, targeting TREM-1 could be a novel therapeutic approach to enhance clearance of the HIV reservoir, at least within the macrophage pools.
Department of Veterans Affairs, Atlanta VAMC, Decatur, GA 30033, USA.|Division of Pulmonary, Allergy, Critical Care &Sleep Medicine, Emory University, Atlanta, GA 30322, USA.
Zhihong
Z
Yuan
Division of Pulmonary, Allergy, Critical Care &Sleep Medicine, Emory University, Atlanta, GA 30322, USA.
Xian
X
Fan
Division of Pulmonary, Allergy, Critical Care &Sleep Medicine, Emory University, Atlanta, GA 30322, USA.
Bashar
B
Staitieh
Department of Veterans Affairs, Atlanta VAMC, Decatur, GA 30033, USA.
Chetna
C
Bedi
Deparment of Pediatrics, Pediatric Infectious Diseases, Emory University, Atlanta, GA 30322, USA.
Paul
P
Spearman
Department of Veterans Affairs, Atlanta VAMC, Decatur, GA 30033, USA.|Division of Pulmonary, Allergy, Critical Care &Sleep Medicine, Emory University, Atlanta, GA 30322, USA.
David M
DM
Guidot
Department of Veterans Affairs, Atlanta VAMC, Decatur, GA 30033, USA.|Division of Pulmonary, Allergy, Critical Care &Sleep Medicine, Emory University, Atlanta, GA 30322, USA.
Ruxana T
RT
Sadikot
D002470:Cell Survival; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000502:physiology / Q000821:virology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000378:metabolism*; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D015699:HIV Envelope Protein gp120; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C514793:gp120 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus