4.7 Article

Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 223, Issue 3, Pages 527-535

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiaa374

Keywords

cutaneous leishmaniasis; Leishmania braziliensis; Leishmania skin test; IFN-gamma; TNF; Th1 immune response; inflammation; IL-1 beta

Funding

  1. National Institutes of Health [AI 136032]

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In patients with negative LST, there is a lower cure rate and impaired Th1 response, as well as an increased frequency of CD8(+) T cells and reduced inflammation in lesions. Restoration of Th1 response is associated with cure of the disease. Increased production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology in LST-negative patients.
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-1 beta (IL-1 beta), 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.

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