title: Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India.
abstract: Post-kala-azar dermal leishmaniasis (PKDL) is a chronic dermal complication that occurs usually after recovery from visceral leishmaniasis (VL). The disease manifests into macular, papular and/or nodular clinical types with mono- or polymorphic presentations. Here, we investigated differences in immunological response between these two distinct clinical forms in Indian PKDL patients. Peripheral blood mononuclear cells of PKDL and naive individuals were exposed in vitro to total soluble Leishmania antigen (TSLA). The proliferation index was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based lymphoproliferative assay. Cytokines and granzyme B levels were determined by cytometric bead array. Parasite load in tissue biopsy samples of PKDL was quantified by quantitative polymerase chain reaction (qPCR). The proportion of different lymphoid subsets in peripheral blood and the activated T cell population were estimated using flow cytometry. The study demonstrated heightened cellular immune responses in the polymorphic PKDL group compared to the naive group. The polymorphic group showed significantly higher lymphoproliferation, increased cytokines and granzyme B levels upon TSLA stimulation, and a raised proportion of circulating natural killer (NK) T cells against naive controls. Furthermore, the polymorphic group showed a significantly elevated proportion of activated CD4(+) and CD8(+) T cells upon in-vitro TSLA stimulation. Thus, the polymorphic variants showed pronounced cellular immunity while the monomorphic form demonstrated a comparatively lower cellular response. Additionally, the elevated level of both activated CD4(+) and CD8(+) T cells, coupled with high granzyme B secretion upon in-vitro TSLA stimulation, indicated the role of cytotoxic cells in resistance to L. donovani infection in polymorphic PKDL.
authors.affiliation: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
authors.forename: H
authors.initials: H
authors.lastname: Kaushal
authors.affiliation: Institut de Recherche pour le Développement, Montpellier.
authors.forename: R
authors.initials: R
authors.lastname: Bras-Gonçalves
authors.affiliation: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
authors.forename: K
authors.initials: K
authors.lastname: Avishek
authors.affiliation: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
authors.forename: D
authors.initials: D
authors.lastname: Kumar Deep
authors.affiliation: Institut de Recherche pour le Développement, Montpellier.
authors.forename: E
authors.initials: E
authors.lastname: Petitdidier
authors.affiliation: Institut de Recherche pour le Développement, Montpellier.
authors.forename: J-L
authors.initials: JL
authors.lastname: Lemesre
authors.affiliation: Virbac, Carros, France.
authors.forename: G
authors.initials: G
authors.lastname: Papierok
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, India.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Dermatology, VMMC and Safdarjung Hospital, New Delhi, India.
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.affiliation: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
authors.forename: P
authors.initials: P
authors.lastname: Salotra
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007194:India; D007694:Killer Cells, Natural / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007893:Leishmania donovani / Q000276:immunology / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000175:diagnosis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007898:Leishmaniasis, Visceral / Q000175:diagnosis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D059208:Parasite Load; D061251:Primary Cell Culture; D012867:Skin / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; C509213:GZMB protein, human; D053804:Granzymes
keywords: granzyme B; leishmania; monomorphic; polymorphic; post-kala-azar dermal leishmaniasis