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, suggesti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3378621?pdf=render |
| _version_ | 1819118090584064000 |
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| author | Gajendra Kumar Katara Nasim Akhtar Ansari Avninder Singh V Ramesh Poonam Salotra |
| author_facet | Gajendra Kumar Katara Nasim Akhtar Ansari Avninder Singh V Ramesh Poonam Salotra |
| author_sort | Gajendra Kumar Katara |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T05:43:21Z |
| format | Article |
| id | doaj.art-ddb31eb562394610aa261c79d618ebd2 |
| institution | Directory Open Access Journal |
| issn | 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T05:43:21Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-ddb31eb562394610aa261c79d618ebd22022-12-21T18:37:07ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27352012-01-0166e170310.1371/journal.pntd.0001703Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL).Gajendra Kumar KataraNasim Akhtar AnsariAvninder SinghV RameshPoonam SalotraBACKGROUND: 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.http://europepmc.org/articles/PMC3378621?pdf=render |
| spellingShingle | Gajendra Kumar Katara Nasim Akhtar Ansari Avninder Singh V Ramesh Poonam Salotra Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). PLoS Neglected Tropical Diseases |
| title | Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). |
| title_full | Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). |
| title_fullStr | Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). |
| title_full_unstemmed | Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). |
| title_short | Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL). |
| title_sort | evidence for involvement of th17 type responses in post kala azar dermal leishmaniasis pkdl |
| url | http://europepmc.org/articles/PMC3378621?pdf=render |
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