Single nucleotide polymorphisms in genes involved in immune responses and outcome of tegumentary leishmaniasis.

Leishmaniases are neglected tropical diseases with a broad clinical spectrum. Tegumentary leishmaniasis (TL) is a disease caused by different Leishmania species, transmitted by phlebotomine sand flies and distributed worldwide. TL can present a cutaneous (CL) or mucocutaneous (MCL) clinical form depending on factors inherent to the parasite, the host and the vector. Polymorphisms in the immune response genes are host genetic factors that influence the pathogenesis or control of leishmaniasis. Single nucleotide polymorphisms (SNPs) in immune genes have been evaluated in several countries where leishmaniasis is endemic. In this review, we report studies on SNPs in several immune genes that might be associated with susceptibility or resistance to TL. We summarize studies from around the world and in Brazil, highlight the difficulties of these studies and future analyses needed to enhance our knowledge regarding host genetic factors in TL. Understanding the genetic characteristics of the host that facilitate resistance or susceptibility to leishmaniasis can contribute to the development of immunotherapy schedules for this disease. The current treatment methods are toxic, and no human vaccine is available.

A Critical Overview of Interleukin 32 in Leishmaniases.

Interleukin-32 (IL-32) has several immune regulatory properties, which have driven its investigation in the context of various diseases. IL-32 expression is reported to be induced in the lesions of patients with American tegumentary leishmaniasis (ATL) by the New World Leishmania spp. that are responsible for causing ATL and visceral leishmaniasis (VL). IL-32 expression may elevate the inflammatory process through the induction of pro-inflammatory cytokines and also via mechanisms directed to kill the parasites. The genetic variants of IL-32 might be associated with the resistance or susceptibility to ATL, while different isoforms of IL-32 could be associated with distinct T helper lymphocyte profiles. IL-32 also determines the transcriptional profile in the bone marrow progenitor cells to mediate the trained immunity induced by ß-glucan and BCG, thereby contributing to the resistance against Leishmania. IL-32γ is essential for the vitamin D-dependent microbicidal pathway for parasite control. In this context, the present review report briefly discusses the data retrieved from the studies conducted on IL-32 in leishmaniasis in humans and mice to highlight the current challenges to understanding the role of IL-32 in leishmaniasis.

New world Leishmania spp. infection in people living with HIV: Concerns about relapses and secondary prophylaxis.

Coinfection with the human immunodeficiency virus (HIV) and Leishmania impairs immune responses, increases treatment failure and relapse rates in patients with American tegumentary leishmaniasis (ATL), as well as visceral leishmaniasis (VL). There is insufficient data on the treatment, relapse, and secondary prophylaxis in patients coinfected with HIV/Leishmania in Brazil. This study investigated patients with HIV/ATL and HIV/VL to describe the outcome of leishmaniasis in patients assisted at a referral hospital of Brazilian midwestern region. Patients with HIV/ATL (n = 21) mainly presented cutaneous diseases (76.2%) with an overall relapse rate of 28.57% after treatment, whereas HIV/VL (n = 28) patients accounted for 17.5% of the cases. The counts of CD4+ T cells and CD8+ T cells and the CD4+/CD8+ cell ratios at diagnosis or relapses were not significantly different between relapsing and non-relapsing patients. Patients with HIV/ATL or HIV/VL showed high levels of activation markers in CD4+ and CD8+ T cells. The regular use of highly active antiretroviral therapy (HAART) and viral load at the time of diagnosis did not influence the relapse rates. Relapses occurred in 36.4% (4/11) of the patients with HIV/VL receiving secondary prophylaxis and in 5.9% (1/17) of the patients who did not receive secondary prophylaxis (p = 0.06). These data are relevant for the therapeutic management of the patients coinfected with HIV/Leishmania.

Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients.

OBJECTIVE: Multiple sclerosis (MS) is a multifactorial chronic disease that affects the central nervous system (CNS). Toll-like receptors (TLRs) play a central role in cytokine production after pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and contribute to CNS damage in MS patients. Here, we evaluated the effects of interferon (IFN)-ß treatment in TLR2 and TLR4-dependent cytokine production and mRNA expression in whole-blood cell cultures from MS patients. METHODS: We evaluated cytokine production by ELISA from whole-blood cell culture supernatants and mRNA expression by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). RESULTS: In patients treated with IFN-ß, tumor necrosis factor (TNF)-α production after exposure to TLR2 agonist (Pam3Cys) was lower than in healthy controls and untreated MS patients. However, IFN-ß treatment had no significant effect on TNF-α production after TLR4 agonist (LPS) stimulation. On the other hand, interleukin (IL)-10 production was increased in TLR4- but not in TLR2-stimulated whole-blood cell culture from MS patients under IFN-ß treatment when compared to the controls. No differences in TNF-α or IL-10 mRNA expression in PBMCs from healthy controls and untreated or treated MS patients were detected, although PBMCs from treated patients presented higher levels of IL-32γ mRNA than those from controls. CONCLUSIONS: Our data suggest that IFN-ß treatment alters the TLR-dependent immune response of PBMCs from MS patients. This may contribute to the beneficial effects of IFN-ß treatment.