Evidence for involvement of th17 type responses in post kala azar dermal leishmaniasis (pkdl)

Background: post kala-azar dermal leishmaniasis (pkdl),a dermal sequel of visceral leishmaniasis,caused by leishmania donovani,constitutes an important reservoir for the parasite. parallel functioning of counter acting immune responses (th1/th2) reflects a complex immunological scenario,suggesting the involvement of additional regulatory molecules in the disease pathogenesis. methodology/principal findings: in the present study,human cytokine/chemokine/receptor specific cdna array technique was employed to identify modulations in gene expression of host immuno-determinants during pkdl,followed by evaluation of th17 type responses by analyzing mrna and protein expression of th17 markers (il-23,il-17,rorγt) and performing functional assays using leishmania antigen (tsla) or recombinant (rec)il-17. array analysis identified key immuno-regulatory molecules including cytokines (tnf-α,ifn-γ,il-10,il-17),chemokines (mcp-1,mip-1α),apoptotic molecules (fasl,trail,irf-1) and receptors (cd40,fas). up regulation in lesional expression of th17 markers was observed during pkdl compared to control (il-17 and il-23,p = 0.0008; rorγt,p = 0.02). in follow-up samples,chemotherapy significantly down regulated expression of all markers. in addition,lesional expression of il-17 was confirmed at protein level by immuno-histochemistry. further,systemic presence of th17 responses (il-17 and il-23) was observed in plasma samples from pkdl patients. in functional assays,tsla stimulated the secretion of il-17 and il-23 from pbmcs of pkdl patients,while recil-17 enhanced the production of tnf-α as well as nitric oxide (no) in pkdl compared to control (tnf-α,p = 0.0002; no,p = 0.0013). further,a positive correlation was evident between lesional mrna expression of il-17 and tnf-α during pkdl. conclusion/significance: the results highlight key immune modulators in pkdl and provide evidence for the involvement of th17 type responses in the disease pathogenesis. © 2012 katara et al.