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The genesis of these diseases is believed to be associated with the route (mucosa versus blood) and mode (cell-free versus cell-associated) of primary infection as well as the modulation of dendritic cell (DC) functions. To explore the role of DCs during early HTLV-1 infection in vivo, we used a chimeric HTLV-1 with a replaced envelope gene from Moloney murine leukemia virus to allow HTLV-1 to fuse with murine cells, which are generally not susceptible to infection with human retroviruses. We also used a CD11c-diphtheria toxin receptor transgenic mouse model system that permits conditional transient depletion of CD11c+ DCs. We infected these transgenic mice with HTLV-1 using both cell-free and cell-associated infection routes in the absence and presence of DCs. The ablation of DCs led to an enhanced susceptibility to infection with cell-free but not cell-associated HTLV-1 in both CD4 and non-CD4 fractions, as measured by the proviral load. Infection with cell-free virus in the absence of DCs was also found to have increased levels of Tax mRNA in the non-CD4 fraction. Moreover, depletion of DCs significantly dampened the cellular immune response (IFN-\u03b3+CD8+ T cells) against both cell-free and cell-associated virus. These results uniquely differentiate the involvement of DCs in early cell-free versus late cell-associated infection of HTLV-1 and highlight a significant aspect of viral immunopathogenesis related to the progression of adult T cell leukemia and HTLV-1\u2013associated myelopathy\/tropical spastic paraparesis after the initial infection.<\/jats:p>","DOI":"10.4049\/jimmunol.0903226","type":"journal-article","created":{"date-parts":[[2010,4,9]],"date-time":"2010-04-09T22:02:19Z","timestamp":1270850539000},"page":"5553-5561","source":"Crossref","is-referenced-by-count":17,"title":["Depletion of Dendritic Cells Enhances Susceptibility to Cell-Free Infection of Human T Cell Leukemia Virus Type 1 in CD11c-Diphtheria Toxin Receptor Transgenic Mice"],"prefix":"10.1093","volume":"184","author":[{"given":"Saifur","family":"Rahman","sequence":"first","affiliation":[{"name":"Drexel Institute for Biotechnology and Virology Research"},{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharr\u00f3n L","family":"Manuel","sequence":"additional","affiliation":[{"name":"Drexel Institute for Biotechnology and Virology Research"},{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zafar K","family":"Khan","sequence":"additional","affiliation":[{"name":"Drexel Institute for Biotechnology and Virology Research"},{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Acheampong","sequence":"additional","affiliation":[{"name":"Drexel Institute for Biotechnology and Virology Research"},{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Tangy","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Virus Lents, Unit\u00e9 de Recherche Associ\u00e9e, 1930 Centre Nationale de Recherche Scientifique, Institut Pasteur , Paris,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Jain","sequence":"additional","affiliation":[{"name":"Drexel Institute for Biotechnology and Virology Research"},{"name":"Department of Microbiology and Immunology, Center for Cancer Biology and Center for Molecular Virology and Neuroimmunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, PA 19127"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,5,15]]},"reference":[{"key":"2026012806285121900_r1","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases.","volume":"24","author":"Proietti","year":"2005","journal-title":"Oncogene"},{"key":"2026012806285121900_r2","first-page":"1096","article-title":"The risk of development of HTLV-I-associated myelopathy\/tropical spastic paraparesis among persons infected with HTLV-I.","volume":"3","author":"Kaplan","year":"1990","journal-title":"J. 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