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

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.