Cryptosporidium parvum antigens induce mouse and human dendritic cells to generate Th1-enhancing cytokines.
Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhoea, which can be life-threatening in an immunocompromised host. To increase our understanding of the mechanisms that play a role in host immune responses, we investigated the effects of C. parvum antigens on the phenotype of mouse and human dendritic cells (DCs). Cryptosporidium parvum antigens induced DC activation as indicated by upregulation of the maturation marker CD209, as well as by the production of the cytokines interleukin-12 p70, IL-2, IL-1beta, IL-6. In particular, significant increases in the expression of IL-12 p70 were observed from mouse DCs derived from bone marrow in response to solubilized sporozoite antigen and the recombinant cryptosporidial antigens, Cp40 and Cp23. We observed a small but significant increase in IL-18 expression following the exposure to Cp40. We found that the induction of Th1 cytokines was MyD88 dependent (MyD88 knockout mouse DCs were unresponsive). Additionally, both sporozoite preparations (solubilized and live) significantly induced IL-12 production by human monocytic dendritic cells (MoDCs). This finding indicates that solubilized as well as recombinant antigens can induce the maturation of DCs and subsequently initiate an innate immune response.
Atlanta VA Medical Center, Decatur, GA 30033, USA.
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Bedi
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Mead
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D016785:Cryptosporidium parvum / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000953:Antigens, Protozoan; D051792:Basic Helix-Loop-Helix Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C095572:Hand1 protein, mouse