Abstract
The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far. In this study, we identified 940 miRNAs in Leishmania donovani infected macrophages by de novo sequencing out of which levels of 85 miRNAs were found to be consistently modified by parasite infection. Herein, we report the functional characteristics of 10 miRNAs i.e., mir-3620, mir-6385, mir-6973a, mir-6996, mir-328, mir-8113, mir-3473f, mir-763, mir-6540, and mir-1264 that were differentially but constantly regulated in infected macrophages for their role in regulation of macrophage effector functions. The target gene prediction and biological interaction analysis revealed involvement of these miRNAs in various biological processes such as apoptosis inhibition, phagocytosis, drug response, and T cell phenotypic transitions. These findings could contribute for the better understanding of macrophages dysfunction and leishmanial pathogenesis. Further, the identified miRNAs could also be used as biomarker/s in diagnosis, prognosis, and therapeutics of Leishmania infection.
Highlights
Leishmaniasis is considered as neglected tropical disease at present it is prevalent in more than 98 countries and associated with significant mortality and morbidity (Alvar et al, 2012)
We identified 150 Micro RNAs (miRNAs) using de novo sequencing approach, which expression levels were largely altered in L. donovani infected macrophages
We identified a total of 940 miRNAs by de novo sequencing in L. donovani infected macrophages
Summary
Leishmaniasis is considered as neglected tropical disease at present it is prevalent in more than 98 countries and associated with significant mortality and morbidity (Alvar et al, 2012). Out of 53 described species of Leishmania parasites, 20 are known to cause human pathogenesis (Akhoundi et al, 2016). Based on its clinical manifestations, the disease is classified into three types: cutaneous (CL), mucocutaneous (MCL), and visceral (VL) leishmaniasis, which differ in their immunopathologies, degree of morbidity and mortality. 350 million people are at risk worldwide by all three forms with 12 million cases of infection (Akhoundi et al, 2016). Out of three pathogenic states, VL infections are fatal, if left untreated and responsible for ∼40,000 deaths per year, worldwide (Ready, 2014)
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