Immunological perspectives of leishmaniasis

Abstract

Leishmania parasites have been widely used in experimental models to understand generation, maintenance and failure of immune responses underlying resistance and susceptibility to infection. The clinical outcomes of Leishmania infection depend on the infecting species and the immune status of the host. Noticeably most people exposed Leishmania never develop overt disease. Understanding the immunological events that result in failure or successful control of the parasites is fundamental to both design and evaluation of vaccines and therapies against the leishmaniases. Recent studies visualizing immune response to Leishmania major in the skin have given new insights into the different immune cells acting as hosts the parasite during different stage of infection. Control of Leishmania infection and disease progression has been associated with generation of T-helper (Th) 1 and Th2 responses respectively. Though still valid in several aspects, the Th1/Th2 paradigm is an oversimplification in need of revision. Th2 polarization has never explained severity of human leishmanial disease and a number of other T-cell subsets, including regulatory T- and Th17- cells, have important roles in susceptibility and resistance of both experimental and human leishmanial disease. This review gives an updated overview of immunological response considered to be of importance in protection, susceptibility, disease progression and cure of leishmaniasis, with a special emphasis on human diseases.

Class II MHC/Peptide Interaction in Leishmania donovani Infection: Implications in Vaccine Design

“…The antileishmanial immune repertoire is dependent on a variety of factors, such as progression of infection (1), genetic background (2), and interplay of host-protective versus disease-promoting cytokines (3). The L. donovani parasites replicate within macrophages (MFs) and presumably within the dendritic cells (DCs) in the disease model (3).…”

Novel Betulin Derivatives as Antileishmanial Agents with Mode of Action Targeting Type IB DNA Topoisomerase

“…The disease presents a variety of symptoms ranging from self-healing cutaneous lesions through the metastasizing mucocutaneous form to the often-fatal visceralizing form (Olivier et al, 2005). Development of parasites resistant to most commonly used pentavalent antimonials (e.g., glucantime and Pentostam) (Ashutosh et al, 2007) or arsenite (Haimeur et al, 1999), together with lack of available vaccine (Kedzierski, 2010;Nylén and Gautam 2010), pose a threat to cure the disease. This led to treatment with current drugs, such as expensive pentamidine (Mishra et al, 1992), amphotericin B (AmBisome; Astellas Pharma, Deerfield, IL) (Wortmann et al, 2010;Solomon et al, 2011) and the teratogenic drug miltefosine (Impavido; AEterna Zentaris, Quebec, QC, Canada) (Sindermann and Engel, 2006;Seifert et al, 2007).…”

Leishmaniosis: an approach about the immunoglobulins and cytokines involved in infection and vaccination

“…Altos níveis de anticorpos específicos são observados em cães naturalmente infectados, com a forma visceral da doença e em outras formas severas, demonstrando também evidências de que o acúmulo de anticorpos tem correlação com a patologia (Nylén & Gautam, 2010).…”

“…E isso se deve ao fato de que os anticorpos não são efetivos na eliminação do parasito quando o mesmo se localiza no interior do vacúolo parasitóforo (Nylén & Gautam, 2010).…”