{ "abstract": "Background: Post-Kala-Azar Dermal Leishmaniasis (PKDL), a dermal sequel of apparently cured visceral leishmaniasis (VL), presents with macular or polymorphic lesions. A relationship, if any, between immune cell infiltration and cytokines potentially causing tissue-remodelling remains poorly defined, and was the focus of this study. Methodology/principal findings: Skin biopsies along with plasma from PKDL patients and healthy controls were analyzed. Tissue sections were assessed for immune cell subsets (CD8 ⁺ T cells, CD68 ⁺ macrophages, CD20 ⁺ B cells, CD66b⁺ neutrophils), associated cytokines/chemokines, adhesion molecules (E-cadherin, Intercellular Adhesion Molecule-1), extracellular matrix (ECM) proteins (fibronectin, collagen I/IV, laminin), matrix metalloproteinase 9 (MMP9) using immuno-histochemistry/fluorescence, while circulating cytokines/chemokines, and MMP9 were quantified using multiplex assays/ELISA. PKDL lesions exhibited increased cell infiltration, monocytes/macrophages>CD8 ⁺ T cells>> neutrophils >B cells. E-cadherin was significantly downregulated, especially in macular lesions, whereas ICAM-1 was elevated. In both PKDL forms, ECM components were significantly reduced, and correlated inversely with immune cell infiltration. The raised levels of circulating chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, CXCL10, IL-8) positively correlated with their corresponding immune populations; additionally, circulating pro- (TNF-α, IFN-γ, IL-6, IL-1β) inflammatory cytokines and IL-4 was elevated. Additionally, lesional TNF-α, IFN-γ and MMP9 was elevated, and correlated inversely with E-cadherin and ECM proteins. Conclusions/significance: In PKDL lesions, there was an elevated presence of monocytes-macrophages/CD8+ T cells, B cells and neutrophils; the increased presence of their respective chemokines endorsed their homing to lesional sites. Furthermore, the increased presence of dermal MMP9, TNF-α and IFN-γ possibly facilitated the breakdown of E-cadherin and ECM components, which could cause a site-specific loss of melanocytes, and contribute to the hypopigmentation associated with PKDL. Author summary: Post Kala-Azar Dermal Leishmaniasis (PKDL), caused by the digenetic parasite Leishmania donovani, and transmitted by the female sand fly presents as a chronic dermal condition in a subset of apparently cured patients with visceral leishmaniasis. PKDL occurs mainly in East Africa and South Asia in 20–50% and 2.5-20% cases of VL respectively. In South Asia, PKDL presents with nodules, papules and/or macules (polymorphic form) or hypopigmented macules (macular form). Owing to its relatively benign, non-lethal nature, patients with PKDL have a poor health seeking behavior and thereby become mobile reservoirs promoting disease transmission. As patients present with hypopigmented lesions, akin to Leprosy, another NTD, they face stigmatization and ostracization. In the absence of an animal model for PKDL, factors involved in the pathogenesis of this hypopigmentation remain poorly defined. Skin biopsies and plasma from patients with polymorphic and macular PKDL were evaluated to understand whether the infiltration of immune cells had any impact on the skin architecture and vice versa. PKDL lesions were characterized by dense immune cell infiltration driven by elevated chemokines and adhesion molecules, particularly ICAM-1. Concomitantly, there is a profound disruption of the epidermal dermal junction, characterized by reduced E-cadherin along with degradation of key extracellular matrix components, fibronectin, collagen I, collagen IV, and laminin, that singly and/or collectively facilitated immune cell infiltration into lesional sites of PKDL, thus perpetuating the disease. These changes are strongly associated with increased levels of pro-inflammatory cytokines (Tumor necrosis factor-alpha and Interferon-gamma) along with matrix metalloproteinase-9 (MMP9), both locally and systemically. As MMP9 is known to correlate negatively with structural proteins essential for melanocyte adhesion, it provides a possible mechanistic link between inflammation, tissue damage, and hypopigmentation. Together, these findings indicate that MMP9 mediated matrix remodelling is a possible central pathway driving skin pathology and hypopigmentation in PKDL.", "abstract_shown": true, "affiliations": [ "Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India", "Department of Pathology, Institute of Postgraduate Medical Education and Research, Kolkata, India", "Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, India", "Department of Microbiology, Sarat Chandra Chattopadhyay Government Medical College and Hospital, Howrah, India", "Department of Dermatology, College of Medicine and Sagore Dutta Hospital, Kolkata, India", "Multidisciplinary Research Unit (MRU), Institute of Postgraduate Medical Education and Research, Kolkata, India" ], "article_type": "Research Article", "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0 ], "name": "Deep Goswami" }, { "affs": [ 1 ], "name": "Shriya Saha" }, { "affs": [ 2 ], "name": "Madhurima Roy" }, { "affs": [ 3 ], "name": "Ebrahim Mohammad" }, { "affs": [ 4 ], "name": "Ratnaprabha Maji" }, { "affs": [ 5 ], "name": "Ritika Sengupta" }, { "name": "Shilpa Sengupta" }, { "name": "Sutopa Roy" }, { "name": "Surya Jyati Chaudhuri" }, { "name": "Nilay Kanti Das" }, { "name": "Bidhan Chakraborty" }, { "name": "Uttara Chatterjee" }, { "name": "Mitali Chatterjee" } ], "bibtex": "https://research.draconitic.com/paper/6xhe41436ndr6.bib", "cited_by": 0, "doi": "10.1371/journal.pntd.0014798", "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014798", "id": "6xhe41436ndr6", "issns": [ "1935-2735", "1935-2727" ], "landing_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014798", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2739|Research on Leishmaniasis Studies" ], [ "plos", "/Biology and life sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Chromatophores/Melanocytes" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Collagens" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular structures and organelles/Extracellular matrix" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Neutrophils" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Epithelial cells/Chromatophores/Melanocytes" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Neutrophils" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Neutrophils" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Medicine and health sciences/Anatomy/Biological tissue/Epithelium/Epithelial cells/Chromatophores/Melanocytes" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Neutrophils" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Zoonoses/Leishmaniasis" ], [ "plos", "/Medicine and health sciences/Medical conditions/Parasitic diseases/Protozoan infections/Leishmaniasis" ], [ "plos", "/Medicine and health sciences/Medical conditions/Tropical diseases/Neglected tropical diseases/Leishmaniasis" ], [ "plos", "/Medicine and health sciences/Surgical and invasive medical procedures/Biopsy" ] ], "openalex": "W7222719333", "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014798&type=printable", "pmcid": "PMC13674725", "pmid": null, "published": "2026-10-01", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/6xhe41436ndr6.ris", "sources": [ { "first_seen": "2026-10-30T12:17:23Z", "native_id": "10.1371/journal.pntd.0014798", "source": "plos", "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014798" }, { "first_seen": "2026-10-30T12:18:29Z", "native_id": "PMC:PMC13674725", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13674725" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "Immune-mediated remodelling of tissue architecture in Post-Kala-Azar Dermal Leishmaniasis (PKDL)", "title_text": "Immune-mediated remodelling of tissue architecture in Post-Kala-Azar Dermal Leishmaniasis (PKDL)", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:29Z", "url": "https://research.draconitic.com/paper/6xhe41436ndr6", "venue": "PLOS Neglected Tropical Diseases", "versions": [] }