Analysis of localized immune responses reveals presence of Th17 and Treg cells in cutaneous leishmaniasis due to Leishmania tropica.

PURPOSE: The interaction between the Leishmania parasite and the host cell involves complex, multifaceted processes. The disease severity in cutaneous leishmaniasis (CL) is largely dependent on the causative species. Most of the information on immune responses in human CL is available with respect to L. major infection and is lacking for L. tropica species. In this study, we employed cytokine/chemokine/receptor membrane cDNA array to capture comprehensive picture of immuno-determinants in localized human tissue during L. tropica infection. Expression of selected molecules was evaluated by real time PCR in dermal lesion tissues at pre- and post treatment stages. Plasma IL-17 level was estimated by sandwich ELISA. RESULTS: The cDNA array analysis identified several immuno-determinants in tissue lesions of Indian CL including cytokines (IFN-γ, TNF-α, IL-1ß, IL-10, IL-13), chemokines (IL-8, CCL2, CCL3, CCL4) and apoptotic molecules (Fas, TRAIL, IRF-1). Elevated mRNA levels of Th17 (IL-17, IL-23 and RORγt) and Treg (CD25, CTLA-4 and Foxp3) markers were observed in lesion tissues of CL patients compared to the control group, which subsided post treatment. Plasma IL-17 levels were found to be significantly higher in CL samples compared to controls. CONCLUSIONS: In addition to defining comprehensive immunological responses inside lesion tissues of CL patients, our study demonstrated the presence of Th17 and Treg cells in CL caused by L. tropica.

A patient presenting with diffuse cutaneous leishmaniasis (DCL) as a first indicator of HIV infection in India.

Opportunistic parasitic infections such as leishmaniasis are common in human immunodeficiency virus (HIV)-infected patients and are usually acquired several days after initial diagnosis of HIV infection. Here, we report on a patient who presented with diffuse cutaneous leishmaniasis (DCL) caused by Leishmania tropica as the first and only clinical manifestation of HIV infection. To the best of our knowledge, this is the first case that illustrates that DCL could be the first clinical indicator of HIV infection. Cutaneous leishmaniasis (CL) and DCL are becoming frequent opportunistic infections in HIV-infected individuals throughout the world. To date, all documented cases of CL and HIV coinfections have been reported in patients who were known cases of HIV and who subsequently developed CL. In this report, we present a case that illustrates that DCL could be the first clinical indicator of HIV infection.

Correlation of parasitic load with interleukin-4 response in patients with cutaneous leishmaniasis due to Leishmania tropica.

We have established the association between parasite burden and localized immune response in patients with cutaneous leishmaniasis (CL) caused by Leishmania tropica. Real-time PCR was used to measure parasitic load in tissue lesions of CL patients at the pretreatment (n=26) and at the post-treatment stage (n=10). Leishmania tropica was detected in all CL lesions with a mean value of 118 357 parasites g(-1) of dermal tissue. Following treatment, only one out of 10 patients showed residual parasites (100 parasites g(-1) tissue). Parasite load was high (mean, 306 000 parasites g(-1) tissue) in acute infections (early lesions) and low (mean, 1081 parasites g(-1) tissue) in chronic infections (late lesions). Intralesional transcripts of interferon-gamma, tumour necrosis factor-alpha, interleukin-1beta (IL-1beta), IL-8, IL-10 and IL-4 were investigated in early lesions (2 months, n=15) by reverse transcriptase-PCR, where IL-4 was found to be significantly upregulated in early lesions (P<0.02). Further, the levels of parasite burden and IL-4 were distinctly correlated in various clinical forms of CL. Other cytokines were at comparable levels in early/late lesions and in different clinical forms. Upregulation of IL-4 was correlated with a higher parasite burden in early lesions of CL, which may be involved in the pathogenesis of CL by inhibiting a protective immune response.