CXC chemokine-mediated protection against visceral leishmaniasis: involvement of the proinflammatory response.
Visceral leishmaniasis, caused by the protozoan parasite Leishmania donovani, is characterized by the loss of ability of the host to generate an effective immune response. In the present study, the comparative potential of CXC chemokines, interferon-gamma-inducible protein-10 (IP-10) and interleukin-8 (IL-8) in restricting Leishmania donovani infection via the release of nitric oxide and proinflammatory cytokines was studied in an in vitro model. Nitric oxide, a crucial mediator for IP-10-mediated leishmanicidal activity, was found to be dependent on inducible nitric oxide synthase 2 (iNOS2) expression and was linked to the mitogen-activated protein kinases (MAPK) signaling pathway. Further, IP-10 was also able to abrogate the survival of Leishmania in an in vivo model of visceral leishmaniasis by restoration of Th1 cytokines and nitric oxide. Thus, this study strongly demonstrates that IP-10, like CC chemokines, is involved in rendering a protective response in visceral leishmaniasis via up-regulation of proinflammatory mediators.
Gupta
Gaurav
G
Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VII-M, Kolkata, India.
Bhattacharjee
Surajit
S
Bhattacharyya
Sandip
S
Bhattacharya
Parna
P
Adhikari
Anupam
A
Mukherjee
Asok
A
Bhattacharyya Majumdar
Suchandra
S
Majumdar
Subrata
S
D000818:Animals; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007893:Leishmania donovani / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D019743:Chemokines, CXC; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020929:Mitogen-Activated Protein Kinase Kinases