{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:34:47Z","timestamp":1788471287906,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Leprosy is a chronic but treatable infectious disease caused by the intracellular pathogen<jats:italic>Mycobacterium leprae<\/jats:italic>. Host immunity to<jats:italic>M. leprae<\/jats:italic>determines the diversity of clinical manifestations seen in patients, from tuberculoid leprosy with robust production of Th1-type cytokines to lepromatous disease, characterized by elevated levels of Th2-type cytokines and a suboptimal proinflammatory response. Previous reports have indicated that<jats:italic>M. leprae<\/jats:italic>is a poor activator of macrophages and dendritic cells in vitro. To understand whether<jats:italic>M. leprae<\/jats:italic>fails to elicit an optimal Th1 immune response or actively interferes with its induction, we have examined the early interactions between<jats:italic>M. leprae<\/jats:italic>and monocytes from healthy human donors. We found that, in nai\u0308ve monocytes,<jats:italic>M. leprae<\/jats:italic>induced high levels of the negative regulatory molecules MCP-1 and interleukin-1 (IL-1) receptor antagonist (IL-1Ra), while suppressing IL-6 production through phosphoinositide-3 kinase (PI3K)-dependent mechanisms. In addition, low levels of proinflammatory cytokines were observed in association with reduced activation of nuclear factor-\u03baB (NF-\u03baB) and delayed activation of IL-1\u03b2-converting enzyme, ICE (caspase-1), in monocytes stimulated with<jats:italic>M. leprae<\/jats:italic>compared with<jats:italic>Mycobacterium bovis<\/jats:italic>BCG stimulation. Interestingly, although in itself a weak stimulator of cytokines,<jats:italic>M. leprae<\/jats:italic>primed the cells for increased production of tumor necrosis factor alpha and IL-10 in response to a strongly inducing secondary stimulus. Taken together, our results suggest that<jats:italic>M. leprae<\/jats:italic>plays an active role to control the release of cytokines from monocytes by providing both positive and negative regulatory signals via multiple signaling pathways involving PI3K, NF-\u03baB, and caspase-1.<\/jats:p>","DOI":"10.1128\/iai.00816-09","type":"journal-article","created":{"date-parts":[[2009,10,20]],"date-time":"2009-10-20T00:59:02Z","timestamp":1256000342000},"page":"293-300","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["<i>Mycobacterium leprae<\/i>Actively Modulates the Cytokine Response in Nai\u0308ve Human Monocytes"],"prefix":"10.1128","volume":"78","author":[{"given":"Daniel","family":"Sinsimer","sequence":"first","affiliation":[{"name":"Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute Center, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"},{"name":"Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Fallows","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute Center, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blas","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute Center, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Krahenbuhl","sequence":"additional","affiliation":[{"name":"National Hansen's Disease Programs Laboratory Research Branch, Louisiana State University, Baton Rouge, Louisiana 70803"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilla","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute Center, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Manca","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute Center, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1","volume":"68","year":"2000","unstructured":"Adams, L. 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