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It is well established that peripheral monocytes differentiate into dendritic cells (DCs) both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>and that monocytes are the<jats:italic>in vivo<\/jats:italic>precursors of mucosal CD103<jats:sup>\u2212<\/jats:sup>proinflammatory DCs. In this study, we asked whether CT had any effects on the differentiation of monocytes into DCs. We found that CT-treated monocytes, in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), failed to differentiate into classical DCs (CD14<jats:sup>low<\/jats:sup>CD1a<jats:sup>high<\/jats:sup>) and acquired a macrophage-like phenotype (CD14<jats:sup>high<\/jats:sup>CD1a<jats:sup>low<\/jats:sup>). Cells differentiated in the presence of CT expressed high levels of major histocompatibility complex class I (MHC-I) and MHC-II and CD80 and CD86 costimulatory molecules and produced larger amounts of IL-1\u03b2, IL-6, and IL-10 but smaller amounts of tumor necrosis factor alpha (TNF-\u03b1) and IL-12 than did monocytes differentiated into DCs in the absence of CT. The enzymatic activity of CT was found to be important for the skewing of monocytes toward a macrophage-like phenotype (Ma-DCs) with enhanced antigen-presenting functions. Indeed, treatment of monocytes with scalar doses of forskolin (FSK), an activator of adenylate cyclase, induced them to differentiate in a dose-dependent manner into a population with phenotype and functions similar to those found after CT treatment. Monocytes differentiated in the presence of CT induced the differentiation of nai\u0308ve T lymphocytes toward a Th2 phenotype. Interestingly, we found that CT interferes with the differentiation of monocytes into DCs<jats:italic>in vivo<\/jats:italic>and promotes the induction of activated antigen-presenting cells (APCs) following systemic immunization.<\/jats:p>","DOI":"10.1128\/iai.01181-10","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T04:43:35Z","timestamp":1292301815000},"page":"1300-1310","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Cholera Toxin Impairs the Differentiation of Monocytes into Dendritic Cells, Inducing Professional Antigen-Presenting Myeloid Cells"],"prefix":"10.1128","volume":"79","author":[{"given":"Filippo","family":"Veglia","sequence":"first","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanita\u0300, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Sciaraffia","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanita\u0300, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riccomi","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanita\u0300, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanita\u0300, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella R. 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