Reorganization of the cutaneous immune microenvironment in tegumentary Leishmaniasis-HIV coinfection: a multiparametric in situ immunohistochemical analysis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Reorganization of the cutaneous immune microenvironment in tegumentary Leishmaniasis-HIV coinfection: a multiparametric in situ immunohistochemical analysis.
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