{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:19:13Z","timestamp":1761801553065,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute, Ricerca Finalizzata","award":["2020-12371760"],"award-info":[{"award-number":["2020-12371760"]}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute Ricerca Finalizzata","doi-asserted-by":"publisher","award":["COVID-2020-12371817"],"award-info":[{"award-number":["COVID-2020-12371817"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute, Ricerca Corrente 5 \u00d7 1000 progetto","doi-asserted-by":"publisher","award":["VISION 08069621"],"award-info":[{"award-number":["VISION 08069621"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ricerca Corrente Fondazione IRCCS Policlinico San Matteo","doi-asserted-by":"publisher","award":["80728"],"award-info":[{"award-number":["80728"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU","award":["PE00000007, CUP F13C22001220007","PE00000007, CUP B73C22001230006"],"award-info":[{"award-number":["PE00000007, CUP F13C22001220007","PE00000007, CUP B73C22001230006"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health, Rome, Italy","doi-asserted-by":"publisher","award":["2799073"],"award-info":[{"award-number":["2799073"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU"},{"name":"Unione europea-Next Generation EU, Missione 4 Componente 1","award":["CUP B53D23016490001"],"award-info":[{"award-number":["CUP B53D23016490001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immunosuppressive therapies used in clinics to reduce the risk of rejection in transplanted patients unfortunately also decrease the response of the immune system to the pathogens. Previous data has shown that the most diffuse SARS-CoV-2 variants of concern between 2020 and 2021 showed a different modulation of the host immune response in healthy subjects, with the Delta B.1.617.2 variant leading to a failure in the activation of the adaptive immune response. In this study, the transcriptomic profiles of monocyte-derived macrophages (MDM), isolated from four immunosuppressed kidney transplant patients and exposed to SARS-CoV-2 VOCs, were analyzed and compared with previously published data gathered from immune-competent subjects. Human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of four kidney transplant patients admitted to the IRCCS Policlinico San Matteo of Pavia (Italy), differentiated into macrophages, and exposed to the active and the UV-inactivated particles of the different SARS-CoV-2 VOCs (D614G, Alpha B.1.1.7, Gamma P.1, Delta B.1.617.2 and Omicron BA.1). Bulk RNA-Seq was performed and significant transcripts were assessed based on Student\u2019s t-test (p-value &lt; 0.05) and Fold change &gt; 2. RNA-Seq data analyses of immunosuppressed MDMs showed that SARS-CoV-2 VOCs, although transcriptionally active, did not induce strong alterations in the transcriptomic profiles of these cells, while a strong down-regulation of key genes involved in the innate immunity pathways was observed when comparing these data to the ones obtained from immunocompetent participants. Overall, this study suggests that patients under immunosuppressive therapies do have an altered macrophage response to SARS-CoV-2 viral infection.<\/jats:p>","DOI":"10.3390\/ijms262110489","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"10489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Attenuated Molecular Response to SARS-CoV-2 in MDMs Isolated from Immunosuppressed Transplanted Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1787-552X","authenticated-orcid":false,"given":"Roberta","family":"Vazzana","sequence":"first","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e8 Camilla","family":"Sammartino","sequence":"additional","affiliation":[{"name":"Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Universit\u00e0 Degli Studi di Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-7257","authenticated-orcid":false,"given":"Nicola","family":"Cuscino","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4566-261X","authenticated-orcid":false,"given":"Roberto","family":"Giambruno","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council, 90146 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-1781","authenticated-orcid":false,"given":"Claudia","family":"Carcione","sequence":"additional","affiliation":[{"name":"Fondazione Ri.MED, 90133 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-9909","authenticated-orcid":false,"given":"Vitale","family":"Miceli","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-935X","authenticated-orcid":false,"given":"Matteo","family":"Bulati","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Agnese","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-7622","authenticated-orcid":false,"given":"Daniele","family":"Lilleri","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-8005","authenticated-orcid":false,"given":"Pier Giulio","family":"Conaldi","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[{"name":"Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Universit\u00e0 Degli Studi di Pavia, 27100 Pavia, Italy"},{"name":"Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3385-2088","authenticated-orcid":false,"given":"Irene","family":"Cassaniti","sequence":"additional","affiliation":[{"name":"Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Universit\u00e0 Degli Studi di Pavia, 27100 Pavia, Italy"},{"name":"Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, 27100 Pavia, 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