Universität zu Köln

Mukherjee, Shibabrata ORCID: 0000-0003-1654-091X, Sengupta, Ritika ORCID: 0000-0002-6769-126X, Mukhopadhyay, Debanjan ORCID: 0000-0002-8921-4106, Braun, Claudia, Mitra, Sneha, Roy, Susmita, Das, Nilay Kanti, Chatterjee, Uttara, von Stebut-Borschitz, Esther and Chatterjee, Mitali (2019). Impaired activation of lesional CD8(+) T-cells is associated with enhanced expression of Programmed Death-1 in Indian Post Kala-azar Dermal Leishmaniasis. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Post Kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani is the dermal sequel of Visceral Leishmaniasis and importantly, is the proposed disease reservoir. The survival of Leishmania parasites within monocytes/macrophages hinges on its ability to effectively nullify immune activation mechanisms. Thus, delineating the disease-promoting immune mechanisms can facilitate development of immunotherapeutic strategies. Accordingly, in the absence of an animal model, this study aimed to delineate the status of CD8(+) T-cells in patients with PKDL. At disease presentation, the absence of CD4(+) T-cells at lesional sites was concomitant with an overwhelming infiltration of CD8(+) T-cells that demonstrated an absence of Perforin, Granzyme and Zap-70, along with an enhanced expression of Programmed Death-1 (PD-1) and the skin-homing CCL17. Additionally, the lesional CCR4(+) CD8(+) population was associated with an enhanced expression of IL-10 and IL-5. In circulation, the enhanced CD8(+) CCR4(+) T-cell population and raised levels of CCL17/22 was associated with an increased frequency of PD-1, while CD127 was decreased. Taken together, in PKDL, the enhanced plasma and lesional CCL17 accounted for the dermal homing of CD8(+) CCR4(+) T-cells, that along with a concomitant upregulation of PD-1 and IL-10 mediated immune inactivation, emphasizing the need for designing immunotherapies capable of reinvigorating T-cell potency.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mukherjee, Shibabrata UNSPECIFIED orcid.org/0000-0003-1654-091X UNSPECIFIED Sengupta, Ritika UNSPECIFIED orcid.org/0000-0002-6769-126X UNSPECIFIED Mukhopadhyay, Debanjan UNSPECIFIED orcid.org/0000-0002-8921-4106 UNSPECIFIED Braun, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Mitra, Sneha UNSPECIFIED UNSPECIFIED UNSPECIFIED Roy, Susmita UNSPECIFIED UNSPECIFIED UNSPECIFIED Das, Nilay Kanti UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatterjee, Uttara UNSPECIFIED UNSPECIFIED UNSPECIFIED von Stebut-Borschitz, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatterjee, Mitali UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-158943
DOI:	10.1038/s41598-018-37144-y
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CUTANEOUS LEISHMANIASIS; LYMPHOCYTES; EXHAUSTION; INDIVIDUALS; CHEMOKINES; HALLMARKS; CCR4 Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15894