Immunological Predictors of Treatment Response in Human Cutaneous Leishmaniasis
Overview
This study identifies circulating soluble factors and CD8+ mucosal-associated invariant T (MAIT) cells as key immunological indicators of treatment response in human cutaneous leishmaniasis caused by Leishmania braziliensis. Elevated frequencies of circulating CD8+ MAIT cells correlate with increased lesion pathology and treatment refractoriness, while a combined set of soluble plasma factors serve as promising noninvasive predictive markers.
Background
Human cutaneous leishmaniasis (CL) is a neglected tropical disease caused by Leishmania braziliensis, characterized by chronic ulcerative skin lesions that can progress to severe mucosal involvement. Treatment primarily relies on antimonial drugs, but therapeutic efficacy varies widely, with increasing cases of treatment failure and drug resistance. The disease's immunopathogenesis involves complex host–parasite interactions, where the balance of proinflammatory and immunomodulatory cytokines, as well as cytotoxic T-cell activity, influences clinical outcomes. Identifying minimally invasive predictive biomarkers and understanding immune determinants of therapy response remain critical challenges.
Data Highlights
Patient Group
Number of Patients
Treatment Response
Responders
126
Complete lesion reepithelialization at 60 days
Refractory
139
Nonresolved lesions at 60 days
Key Findings
A combined panel of circulating soluble factors in plasma can predict treatment outcomes in human CL noninvasively.
Elevated frequencies of circulating CD8+ MAIT cells are associated with increased lesion pathology and treatment refractoriness.
Gene expression profiling of lesion biopsies reveals a CD8+ MAIT cell-related gene signature in refractory patients.
CD4+ and double-negative T cells contribute to the cytokine milieu that influences protective versus pathogenic immune responses.
Cytotoxic molecules such as granzymes and CD107, linked to CD8+ T-cell activity, play a pivotal role in tissue pathology and treatment efficacy.
Clinical Implications
Monitoring circulating soluble factors alongside CD8+ MAIT cell frequencies may enable early identification of patients at risk for treatment failure, allowing for personalized therapeutic strategies. Incorporating immunomodulatory approaches targeting MAIT cells or cytotoxic pathways could enhance treatment efficacy in refractory cases. These insights support the development of tailored interventions to improve clinical outcomes in human CL.
Conclusion
The study elucidates critical immunological markers, including circulating soluble factors and CD8+ MAIT cells, that predict treatment response in human cutaneous leishmaniasis. These findings provide a foundation for personalized treatment approaches and novel immunomodulatory therapies to address refractory disease.
References
Article Source 2024 -- Immunological Indicators of Treatment Response in Human Cutaneous Leishmaniasis
by Amanda B Figueiredo, Katia L P Morais, Israel T Silva, Lorhenn B L Maia, Jaqueline R Buttura, Bruna D F Barros, Natalia S Alves, Flavio Pignataro-Oshiro, Samara M M Shimon, Andrea Teixeira-Carvalho, Lucas Almeida, Edgar Carvalho, Paulo Machado, Jenefer M Blackwell, Lea Castellucci, Walderez O Dutra, Kenneth J Gollob
