The Innate Immune Response as a Therapeutic Target for Cutaneous Leishmaniasis

The overall goal of the proposed project is to identify innate host functions that contribute to cure or failure during antileishmanial drug therapy, and their related biomarkers. Results from this project enabled the identification of host-specific predictive and prognostic signatures of therapeutic responsiveness, and the bases for rational selection of host-targeted therapeutics that redirect inflammation and revert pathogenicity. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in Cutaneous Leishmaniasis (CL) patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.]]>
Inclusion Criteria:Patients with parasitological diagnosis of cutaneous leishmaniasisTime of lesion evolution < 6 monthsAge between 18 to 60 yearsHemoglobin levels >11 g/dL for women and > 12 g/dL for menVoluntary participation in the study and signed informed consentCandidates for treatment with systemic Glucantime® or miltefosineExclusion Criteria: Mucosal, diffuse or disseminate cutaneous leishmaniasisUse of antileishmanial drugs in the last 13 weeks including pentavalent antimonials, amphotericin B, miltefosine, pentamidine, among othersIn the case of women, positive pregnancy test or breastfeedingMedical history of conditions or use of medications that affect the immune system (e.g. HIV, neoplasm, diabetes mellitus, autoimmune diseases, corticosteroids, immunomodulatory or antineoplastic drugs, etc.) ]]>