Induction of Th1/Th17 immune response by Mycobacterium tuberculosis: role of dectin-1, Mannose Receptor, and DC-SIGN.
Mtb influences DC activity and T cell-mediated immune responses. We show that the treatment of immature monocyte-derived DC with Mtb elicited the formation of mature DC, producing TNF-alpha, IL-1beta, IL-6, and IL-23 and instructing CD4(+) cells to secrete IFN-gamma and IL-17. Mtb-induced cytokine release by DC depended on dectin-1 receptor engagement, whereas MR or DC-SIGN stimulation inhibited this process. A selective dectin-1 binding by the receptor agonist glucan was sufficient to enable DC to generate Th1/Th17 lymphocytes, showing features comparable with those induced by Mtb-treated DC. Interestingly, DC-SIGN or MR engagement inhibited Th17 and increased Th1 generation by glucan- or Mtb-treated DC. Our results indicate that Mtb modulates the lymphocyte response by affecting DC maturation and cytokine release. Dectin-1 engagement by Mtb enables DC to promote a Th1/Th17 response, whereas DC-SIGN and MR costimulation limits dectin-1-dependent Th17 generation and favors a Th1 response, probably by interfering with release of cytokines.
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy.
Elena
E
Zenaro
Marta
M
Donini
Stefano
S
Dusi
D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1