Abstract
The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4+ and CD8+ T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD). Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific TNAIVE cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (TEM for CD4+ T cells and TEMRA for CD8+ T cells). The amount of antigen-specific CD57+/CD8+ TEMRA cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects. Regarding functionality, a more robust multifunctional CD8+ T cell response was detected in cured patients than in those with active cutaneous leishmaniasis. Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ+/granzyme-B/+perforin+). Patients with an active leishmaniosis process had a significantly higher frequency of CD8+ T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients. The expression profile observed in cured patients could be indicative of an imbalance toward a CD8+ Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis. The results also suggest a possible exhaustion process of CD8+ T cells associated with the evolution of Leishmania infection.
Highlights
Leishmaniasis is caused by intracellular parasites belonging to Leishmania species, and 1.5–2 million new cases are reported annually worldwide (WHO, 2016)
Understanding the immunological mechanisms that underlie disease outcomes after the infection of a subject with Leishmania (Viannia) is essential given that there are asymptomatic patients, parasite persistence after treatment and disease reactivation (Saravia et al, 1990)
It has been reported that the clinical cure of leishmaniasis is mainly dependent on T cell populations that secrete Th1-related cytokines (Coutinho et al, 1998; Da-Cruz et al, 2005)
Summary
Leishmaniasis is caused by intracellular parasites belonging to Leishmania species, and 1.5–2 million new cases are reported annually worldwide (WHO, 2016). Depending on the infecting Leishmania species, different clinical manifestations occur, with cutaneous leishmaniasis (CL) being the most prevalent clinical form (de Vries et al, 2015). Systematic studies carried out in different areas of Colombia since the 1980s showed the presence of six species belonging to the genus Leishmania, with a higher prevalence of Leishmania panamensis (50.8–74.5%) and Leishmania braziliensis (15.3–30.3%) isolates than isolates of the other species. It is thought that 97% of the pathologies caused by Leishmania spp. in Colombia correspond to CL (Corredor et al, 1990; Ovalle et al, 2006; Ramírez et al, 2016)
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