Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice.
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 [IFNγ], interleukin12 [IL]12, and IL1β) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFNγ 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.
Department of Animal Biology, School of Life Science, University of Hyderabad, Hyderabad, India.|Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Radheshyam
R
Maurya
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Parna
P
Bhattacharya
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Nevien
N
Ismail
Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Pradeep K
PK
Dagur
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Amritanshu B
AB
Joshi
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Kundan
K
Razdan
Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
J Philip
JP
McCoy
Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Jill
J
Ascher
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Ranadhir
R
Dey
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.
Hira L
HL
Nakhasi
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology*; D020738:Leptin / Q000097:blood / Q000172:deficiency / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000469:parasitology
D007155:Immunologic Factors; D053583:Interleukin-1beta; D020738:Leptin; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma