HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1

Abstract

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.

Peroxisome proliferator‐activated receptor‐γ agonists attenuate biofilm formation by Pseudomonas aeruginosa

“…Total cellular RNA was extracted by using the RNeasy RNA extraction kit (Qiagen, Valencia, CA, USA) and Trizol mRNA extraction kit (Thermo Fisher Scientific) according to manufacturer instructions. cDNA was synthesized from 1 μg or 500 ng total RNA by using the SuperScript first‐strand synthesis system (Thermo Fisher Scientific), as previously described (20, 36).…”

HIV-1 decreases Nrf2/ARE activity and phagocytic function in alveolar macrophages

“…Importantly, these proteins have been demonstrated to have key roles in the disruption of Mf homeostasis in other organ systems [15] as well as in the lung epithelium [16]. In concert with our collaborators, we recently established a role for Tat in preventing Mf apoptosis [17]. We hypothesized, based on those findings, as well as the presence of these viral proteins in bronchoalveolar lavage fluid [14], that Tat and gp120 may well be responsible for defects in AM function.…”

“…Biol. 102: 517-525;2017. Abbreviations: AM = alveolar Mf, ARE = antioxidant response element, ART = antiretroviral therapy, CDDO = 2-cyano-3,12-dixooleana-1,9(11)-dien-28-oic acid, COPD = chronic obstructive pulmonary disease, GCLC = glutamate-cysteine ligase catalytic subunit, Gp120 = glycoprotein 120, HIV-1 Tg = human immunodeficiency virus-1 transgene, Keap1 = Kelch-like ECH-associated protein 1, MDM = monocyte-derived Mf, (continued on next page) 0741-5400/17/0102-517…”

HIV gp120 in the Lungs of Antiretroviral Therapy–treated Individuals Impairs Alveolar Macrophage Responses to Pneumococci

“…Apoptosisassociated killing enhances clearance of pneumococci, limits tissue invasion and downregulates the inflammatory response in the lung (10,11). Importantly, HIV-1 is associated with an anti-apoptotic gene expression profile in monocytes in vivo and promotes macrophage resistance to apoptosis, which contributes to these cells constituting a viral reservoir for HIV-1 (12)(13)(14)(15).…”

“…HIV-1 envelope (gp120) has been shown to be necessary for macrophage resistance to apoptosis acutely after a single cycle of replication with X4-or R5-tropic HIV-1 (13) while gp120 when disassociated from virus, is sufficient to influence macrophage function and apoptosis resistance (14,46,47). Importantly, we observed this effect at concentrations of gp120 similar both to those we found in the BAL and commensurate with those described in other anatomical compartments in HIV-1-seropositive individuals (46).…”