{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T23:33:57Z","timestamp":1768088037167,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>HIV\u20101 eradication is hindered by the presence of inducible long\u2010lived reservoirs of latently infected cells which rapidly disseminate viral particles upon treatment interruption. Eliminating these reservoirs by the so\u2010called shock and kill strategy represents a crucial concept toward an HIV\u20101 cure. Several molecules called latency\u2010reversing agents (LRAs) are under intensive investigations to reactivate virus gene expression. These studies are mainly conducted on CD4<jats:sup>+<\/jats:sup> T cells where LRAs are well tolerated and did not induce global cellular activation. However, despite their broad spectrum, the putative impact of LRAs on other cellular reservoirs such as macrophages is still ill\u2010defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the impact of the protein kinase C (PKC) activator bryostatin\u20101, bromodomain inhibitor JQ1 and histone deacetylase inhibitor romidepsin used either alone or in combination on human primary monocyte\u2010derived macrophages (MDMs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that bryostatin\u20101, JQ1, and romidepsin or their combinations are not toxic at nanomolar concentrations but induce metabolic and morphologic alterations of MDMs. Bryostatin\u20101 triggered the secretion of pro\u2010inflammatory cytokines, while JQ\u20101 decreased it. Phagocytosis and endocytosis were modestly impaired upon bryostatin\u20101 treatment whereas efferocytosis was markedly downregulated by romidepsin. Despite its pro\u2010inflammatory profile, bryostatin\u20101 did not induce classically activated macrophage markers. Finally, we reveal that conditioned medium from bryostatin\u20101\u2010treated macrophages did not potentiate its reactivation feature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study reveals that LRAs can diversely impact basic physiologic features of human primary macrophages and could potentially decrease reactivation of nearby CD4<jats:sup>+<\/jats:sup> T cells latently infected with HIV\u20101. Our observations further stress the need to include different cell populations when assessing HIV\u20101 cure strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.590","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T19:06:55Z","timestamp":1670526415000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of latency\u2010reversing agents on human macrophage physiology"],"prefix":"10.1002","volume":"11","author":[{"given":"Laurent","family":"Hany","sequence":"first","affiliation":[{"name":"Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec\u2010Universit\u00e9 Laval Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc\u2010Olivier","family":"Turmel","sequence":"additional","affiliation":[{"name":"Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre 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