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Am J Trop Med Hyg 2016 Jul 6;95(1):109-19

Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice.

Maurya R, Bhattacharya P, Ismail N, Dagur PK, Joshi AB, Razdan K, McCoy JP Jr, Jill A, Dey R, Nakhasi HL

Abstract

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani There are no vaccines and available drugs against leishmaniasis are toxic. Immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. Therefore, finding novel immunomodulators for VL therapy is a pressing need. This study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the immune response, in L. donovani-infected mice. We observed that recombinant leptin treatment reduced splenic parasite burden compared with non-treated infected normal mice. Decrease in parasite burden correlated with an induction of innate immune response in antigen-presenting cells that showed an increase in nitric oxide, enhanced pro-inflammatory cytokine (interferon gamma [IFN¿], interleukin12 [IL]12, and IL1ß) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFN¿ production from both CD4+ and CD8+ T cells, compared with non-treated infected mice. Alternatively, leptin-deficient (Ob/Ob) mice had higher splenic and liver parasite burden compared with the infected normal mice. However, leptin treatment failed to reduce the splenic parasite burden and improve a host-protective cytokine response in these mice. In addition, in contrast to dendritic cells (DCs) from a normal mouse, Ob/Ob mouse-derived DCs showed a defect in the induction of innate immune response on Leishmania infection that could not be reversed by leptin treatment. Therefore, our findings reveal that leptin has a differential immunomodulatory effect in controlling VL in normal and Ob/Ob mice.


Category: Journal Article
PubMed ID: #27114296 DOI: 10.4269/ajtmh.15-0804
PubMed Central ID: #PMC4944674
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2016-02-19 Entry Last Modified: 2019-06-09
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