Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis. (23rd July 2020)

• Record Type: Journal Article
• Authors: Carvalho, Augusto M; Guimarães, Luiz H; Costa, Rúbia; Saldanha, Maíra G; Prates, Iana; Carvalho, Lucas P; Arruda, Sérgio; Carvalho, Edgar M
• Is Part Of: Journal of infectious diseases. Volume 223:Number 3(2021)
• Page Start: 527
• Page End: 535
• Publication Date: 2020-07-23
• Subjects: cutaneous leishmaniasis -- Leishmania braziliensis -- Leishmania skin test -- IFN-γ -- TNF -- Th1 immune response -- inflammation -- IL-1β; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa374
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients. Methods: We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST. Results: The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8 + T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1β (IL-1β), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response. Conclusions: In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8 + T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology. Abstract : Cutaneous leishmaniasis with negative Leishmania skin test was associated with an impairment of in vitro Th1 response and treatment failure. While, innate inflammation and cytotoxicity was preserved in LST-negative patients, cure was linked to restoration of Th1 response.