Academic Journal
Reorganization of the cutaneous immune microenvironment in tegumentary Leishmaniasis-HIV coinfection: a multiparametric in situ immunohistochemical analysis.
| Τίτλος: | Reorganization of the cutaneous immune microenvironment in tegumentary Leishmaniasis-HIV coinfection: a multiparametric in situ immunohistochemical analysis. |
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| Συγγραφείς: | Xavier MB; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil., Fontes LDS; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil. Electronic address: luccasfontes@gmail.com., Motizuki AK; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil., Alves LRM; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil., Rodrigues GF; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil., Alcântara LDS; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil., Ishikawa EAY; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil., Brito EB; Research Laboratory in Tropical Dermatology and Endemic Diseases, Nucleus of Tropical Medicine, Federal University of Pará, Generalíssimo Deodoro Avenue, Number 92, Belém, Pará, 66055-240, Brazil., Gomes CMC; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil., Corbett CEP; Infectious Diseases Pathology Laboratory (LIM50), Pathology Department, Medical School, São Paulo University, Doctor Arnaldo Avenue, Number 455, São Paulo, São Paulo, 01246-903, Brazil. |
| Πηγή: | Microbial pathogenesis [Microb Pathog] 2026 Sep; Vol. 218, pp. 108672. Date of Electronic Publication: 2026 Jun 30. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; Orlando : Academic Press, c1986- |
| Ιατρικοί όροι (MeSH): | HIV Infections*/immunology , HIV Infections*/drug therapy , HIV Infections*/pathology , HIV Infections*/complications , Coinfection*/immunology , Coinfection*/pathology , Leishmaniasis, Cutaneous*/immunology , Leishmaniasis, Cutaneous*/pathology , Leishmaniasis, Cutaneous*/complications , Skin*/immunology , Skin*/pathology , Cellular Microenvironment*/immunology, Cytokines/metabolism ; Macrophages/immunology ; Dendritic Cells/immunology ; Humans ; Male ; Female ; Adult ; Immunohistochemistry ; Middle Aged ; Antiretroviral Therapy, Highly Active ; Antigens, CD ; Interleukin-1beta ; Nitric Oxide Synthase Type II ; Antigens, Differentiation, Myelomonocytic ; Forkhead Transcription Factors ; Biopsy |
| Περίληψη: | Background: Leishmania-HIV coinfection compromises the cutaneous immune response through mechanisms that remain poorly understood. This exploratory study compared the in situ immune microenvironment of skin lesions between coinfected and non-coinfected patients with American tegumentary leishmaniasis (ATL). Methods: The in situ density of 20 immunohistochemical markers-covering cellular populations, regulatory and pro-inflammatory cytokines, and the inflammasome/pyroptosis axis-was quantified in skin biopsies from 23 patients with ATL: 17 without coinfection and 6 coinfected with HIV. Densities were compared between groups, stratified by highly active antiretroviral therapy (HAART), and explored by principal component analysis. Results: The groups differed in sex distribution and clinical form, and no coinfected patient presented the localized form. Principal component analysis segregated the two immunological profiles. The ATL-HIV group showed reduced densities of CD1a+ dendritic cells, CD4+ and CD20+ lymphocytes, CD68+ macrophages, iNOS+ and CD163+ cells, as well as reduced IL-6+ and IL-1β+ cells. Conversely, FoxP3+, TGF-β+, IFN-γ+, and gasdermin D+ cells were increased. Patients on HAART remained clustered with the other coinfected patients, with no migration toward the ATL group. Conclusions: HIV is associated with a broad reorganization of the cutaneous immune microenvironment in ATL, combining depletion of effector populations, expansion of regulatory pathways, and engagement of alternative pyroptotic activity. These hypothesis-generating findings likely underestimate the functional impact of coinfection and warrant confirmation in larger studies. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Coinfection; Cytokines; HIV infections; Immunohistochemistry; Inflammasomes; Leishmaniasis, Cutaneous; Pyroptosis |
| Substance Nomenclature: | 0 (Cytokines) 0 (Antigens, CD) 0 (Interleukin-1beta) EC 1.14.13.39 (Nitric Oxide Synthase Type II) 0 (Antigens, Differentiation, Myelomonocytic) 0 (Forkhead Transcription Factors) |
| Entry Date(s): | Date Created: 20260630 Date Completed: 20260718 Latest Revision: 20260718 |
| Update Code: | 20260719 |
| DOI: | 10.1016/j.micpath.2026.108672 |
| PMID: | 42379477 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1096-1208 |
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| DOI: | 10.1016/j.micpath.2026.108672 |