{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T21:52:59Z","timestamp":1759009979159},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,2,5]],"date-time":"2008-02-05T00:00:00Z","timestamp":1202169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Research Program on AIDS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, we analyzed the possibility that Indinavir (IDV), a well-known protease inhibitor (PI) used in highly active antiretroviral therapy, could affect immune response against the opportunistic fungus Cryptococcus neoformans. In particular, the quality of dendritic cell (DC) response was analyzed. The results reported here show that IDV treatment induces an expansion of DC with CD8\u03b1 phenotype in spleens of infected hosts. Splenic CD11c+ DC expressed elevated costimulatory molecules such as CD40 and CD80, showed an increased expression of mRNA for proinflammatory cytokines, and secreted abundant IL-12. Integration of all aforementioned regulatory effects results in development of an efficient, T cell-protective response that reflects a consistent reduction in fungus colonization at a cerebral level. These results could help to elucidate the immunoregulatory activity of PI and point out the beneficial effects of IDV in regulating DC functions and antifungal activity. Therefore, although new PI are being introduced in the clinical setting, nevertheless, given its low cost and proven efficacy, IDV could still be considered a potential key compound in the treatment of HIV in resource-limited settings.<\/jats:p>","DOI":"10.1189\/jlb.0707454","type":"journal-article","created":{"date-parts":[[2008,2,6]],"date-time":"2008-02-06T02:35:34Z","timestamp":1202265334000},"page":"1286-1294","source":"Crossref","is-referenced-by-count":7,"title":["Indinavir influences biological function of dendritic cells and stimulates antifungal immunity"],"prefix":"10.1093","volume":"83","author":[{"given":"Eva","family":"Pericolini","sequence":"first","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elio","family":"Cenci","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Gabrielli","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Perito","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Mosci","sequence":"additional","affiliation":[{"name":"Internal Medicine, Department of Pathology, Diagnostic and Veterinary Clinic, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Bistoni","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Vecchiarelli","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,2,5]]},"reference":[{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1128\/iai.30.1.5-11.1980","article-title":"Transfer of immunity to cryptococcosis by T-enriched splenic lymphocytes from Cryptococcus neoformans-sensitized mice","volume":"30","author":"Lim","year":"1980","journal-title":"Infect. Immun."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1056\/NEJM199003083221017","article-title":"Cryptococcal infections in patients with AIDS","volume":"322","author":"Good","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1086\/313757","article-title":"Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America","volume":"30","author":"Saag","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"146","DOI":"10.5694\/j.1326-5377.2007.tb00839.x","article-title":"Ten years of highly active antiretroviral therapy for HIV infection","volume":"186","author":"Chen","year":"2007","journal-title":"Med. J. Aust."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0966-842X(02)02330-2","article-title":"Anti-fungal therapy at the HAART of viral therapy","volume":"10","author":"Munro","year":"2002","journal-title":"Trends Microbiol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1056\/NEJM199606203342516","article-title":"Resolution of refractory AIDS-related mucosal candidiasis after initiation of didanosine plus saquinavir","volume":"334","author":"Zingman","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1053\/jinf.2001.0810","article-title":"The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART) in a London clinic","volume":"42","author":"Ives","year":"2001","journal-title":"J. Infect."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1086\/314871","article-title":"In vitro and in vivo anticandidal activity of human immunodeficiency virus protease inhibitors","volume":"180","author":"Cassone","year":"1999","journal-title":"J. Infect. Dis."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0924-8579(03)00113-4","article-title":"AIDS-associated Cryptococcus infection before and after the highly active antiretroviral therapy era: emerging management problems","volume":"22","author":"Manfredi","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2023033005121666600_","first-page":"418","article-title":"Importance of antiproteases in the treatment of microsporidia and\/or cryptosporidia infections in HIV-seropositive patients","volume":"46","author":"Bobin","year":"1998","journal-title":"Pathol. Biol. (Paris)"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1517\/17425255.3.3.347","article-title":"Indinavir\/ritonavir remains an important component of HAART for the treatment of HIV\/AIDS, particularly in resource-limited settings","volume":"3","author":"Cressey","year":"2007","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1086\/426828","article-title":"Influence of indinavir on virulence and growth of","volume":"191","author":"Monari","year":"2005","journal-title":"Cryptococcus neoformans. J. Infect. Dis."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/13693780500252020","article-title":"Indinavir-treated Cryptococcus neoformans promotes an efficient antifungal immune response in immunosuppressed hosts","volume":"44","author":"Pericolini","year":"2006","journal-title":"Med. Mycol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.smim.2005.05.015","article-title":"Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm","volume":"17","author":"Villadangos","year":"2005","journal-title":"Semin. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/jlb.66.2.242","article-title":"Role of CD8\u03b1+and CD8\u03b1- dendritic cells in the induction of primary immune responses in vivo","volume":"66","author":"Maldonado-Lopez","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4049\/jimmunol.165.1.158","article-title":"Dendritic cells in the induction of protective and nonprotective anticryptococcal cell-mediated immune responses","volume":"165","author":"Bauman","year":"2000","journal-title":"J. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1128\/IAI.69.2.1127-1133.2001","article-title":"Characterization of murine lung dendritic cells infected with","volume":"69","author":"Gonzalez-Juarrero","year":"2001","journal-title":"Mycobacterium tuberculosis. Infect. Immun."},{"key":"2023033005121666600_","first-page":"207","article-title":"Disseminated cryptococcosis presenting as pseudofolliculitis in an AIDS patient","volume":"66","author":"Coker","year":"2000","journal-title":"Cutis"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1002\/eji.200424878","article-title":"Depending on their maturation state, splenic dendritic cells induce the differentiation of CD4(+) T lymphocytes into memory and\/or effector cells in vivo","volume":"34","author":"De Heusch","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1084\/jem.189.3.587","article-title":"CD8\u03b1+and CD8\u03b1- subclasses of dendritic cells direct the development of distinct T helper cells in vivo","volume":"189","author":"Maldonado-Lopez","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1128\/IAI.66.10.4994-5000.1998","article-title":"Interleukin-12 is essential for a protective Th1 response in mice infected with","volume":"66","author":"Decken","year":"1998","journal-title":"Cryptococcus neoformans. Infect. Immun."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/373123a0","article-title":"Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection","volume":"373","author":"Ho","year":"1995","journal-title":"Nature"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/373117a0","article-title":"Viral dynamics in human immunodeficiency virus type 1 infection","volume":"373","author":"Wei","year":"1995","journal-title":"Nature"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/01.qai.0000214809.83218.88","article-title":"Adverse effects of antiretroviral drugs on HIV-1-infected and -uninfected human monocyte-derived macrophages","volume":"42","author":"Azzam","year":"2006","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopha.2005.07.006","article-title":"The dissociation between virological and immunological responses to HAART","volume":"59","author":"Jevtovic","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"176","DOI":"10.2165\/00002018-199615030-00003","article-title":"Treatment of HIV infection. Tolerability of commonly used antiretroviral agents","volume":"15","author":"Notermans","year":"1996","journal-title":"Drug Saf."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"F117","DOI":"10.1097\/00002030-199715000-00001","article-title":"Saquinavir pharmacokinetics alone and in combination with nelfinavir in HIV-infected patients","volume":"11","author":"Merry","year":"1997","journal-title":"AIDS"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/00002030-199801000-00005","article-title":"Improvement of chronic diarrhoea in patients with advanced HIV-1 infection during potent antiretroviral therapy","volume":"12","author":"Foudraine","year":"1998","journal-title":"AIDS"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1097\/00002030-200004140-00014","article-title":"Highly active antiretroviral therapy inhibits cytokine production in HIV-uninfected subjects","volume":"14","author":"Tovo","year":"2000","journal-title":"AIDS"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1002\/eji.200323646","article-title":"The HIV protease inhibitor indinavir reduces immature dendritic cell transendothelial migration","volume":"33","author":"Whelan","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1368-7646(03)00060-8","article-title":"HIV protease inhibitors as new treatment options for Kaposi\u2019s sarcoma","volume":"6","author":"Barillari","year":"2003","journal-title":"Drug Resist. Updat."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0952-7915(02)00365-5","article-title":"How dendritic cells and microbes interact to elicit or subvert protective immune responses","volume":"14","author":"Palucka","year":"2002","journal-title":"Curr. Opin. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1365-2141.2005.05498.x","article-title":"Cytokines and fungal infections","volume":"129","author":"Antachopoulos","year":"2005","journal-title":"Br. J. Haematol"},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"47840","DOI":"10.1074\/jbc.M105582200","article-title":"Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function","volume":"276","author":"Gruber","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/mmy.38.6.407.417","article-title":"Immunoregulation by capsular components of","volume":"38","author":"Vecchiarelli","year":"2000","journal-title":"Cryptococcus neoformans. Med. Mycol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1084\/jem.20040317","article-title":"The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80\/86 costimulation","volume":"199","author":"Fujii","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4049\/jimmunol.178.1.242","article-title":"Cytokine-dependent Blimp-1 expression in activated T cells inhibits IL-2 production","volume":"178","author":"Gong","year":"2007","journal-title":"J. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.4049\/jimmunol.178.9.5753","article-title":"Protection from direct cerebral Cryptococcus infection by interferon-{\u03b3}-dependent activation of microglial dells","volume":"178","author":"Zhou","year":"2007","journal-title":"J. Immunol."},{"key":"2023033005121666600_","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1128\/iai.59.10.3393-3397.1991","article-title":"Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocyte-macrophage colony-stimulating factor to inhibit","volume":"59","author":"Levitz","year":"1991","journal-title":"Cryptococcus neoformans. Infect. Immun."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0707454","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/5\/1286\/49634914\/jlb1286.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/5\/1286\/49634914\/jlb1286.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T07:52:33Z","timestamp":1684223553000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/83\/5\/1286\/6975528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,5]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2008,2,5]]},"published-print":{"date-parts":[[2008,5,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0707454","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,5]]},"published":{"date-parts":[[2008,2,5]]}}}