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‐α, IL‐1β, IL‐6, and IL‐23 and instructing CD4+ cells to secrete IFN‐γ 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.

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