02240nas a2200373   4500000000100000008004100001260001300042653003100055653002500086653002000111653001900131653001100150653002200161653001800183653001900201653001900220653001800239653001200257653002600269653002200295653002400317653002500341653001800366653003200384100001300416700001200429700001200441700001800453245009000471300001200561490000700573520127200580022001401852       2006                            d  c2006 Jun10aCD4-Positive T-Lymphocytes10aCell Differentiation10aDendritic Cells10aFlow Cytometry10aHumans10aImmunophenotyping10aInterleukin-110aInterleukin-1010aInterleukin-1210aInterleukin-610aleprosy10aLymphocyte Activation10aMembrane Proteins10aMycobacterium bovis10aMycobacterium leprae10aPeptidoglycan10aTumor Necrosis Factor-alpha1 aMakino M1 aMaeda Y1 aMukai T1 aKaufmann SH E00aImpaired maturation and function of dendritic cells by mycobacteria through IL-1beta.  a1443-520 v363 a<p>Dendritic cells (DC) are pivotal for initiation and regulation of innate and adaptive immune responses evoked by vaccination and natural infection. After infection, mycobacterial pathogens first encounter monocytes, which produce pro-inflammatory cytokines, including IL-1beta, TNF-alpha and IL-6. The role of these cytokines in DC maturation remains incompletely understood. Here, we show that maturation of DC from monocytes was impaired by pretreatment of monocytes with low doses of IL-1beta. Under these conditions, Mycobacterium leprae-infected DC failed to stimulate antigen-specific T cell responses. Expression of CD86 and CD83 and production of IL-12 in response to lipopolysaccharide and peptidoglycan were diminished. In contrast, these DC functions were not impaired by pretreatment with TNF-alpha, IL-6 or IL-10. When monocytes were infected with M. bovis Bacillus Calmette-Guérin, and subsequently differentiated to DC, the activity of these DC was suppressed as well. Thus, IL-1beta acts at early stages of differentiation of DC and impairs biological functions of DC at later stages. Therefore, production of IL-1beta by mycobacteria-infected antigen-presenting cells counteracts effective stimulation of innate and adaptive immune responses.</p>  a0014-2980