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TLR ‐mediated distinct IFN ‐γ/ IL ‐10 pattern induces protective immunity against murine visceral leishmaniasis
Author(s) -
Paul Joydeep,
Karmakar Subir,
De Tripti
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242428
Subject(s) - biology , immune system , tlr2 , immunology , leishmania donovani , leishmania major , visceral leishmaniasis , leishmania , microbiology and biotechnology , innate immune system , leishmaniasis , parasite hosting , world wide web , computer science
Resistance to murine visceral leishmaniasis ( VL ) correlates with the development of an IFN ‐γ predominant immune response. Beta1,4‐galactose terminal glycans are potent inducers of IFN ‐γ. Here, we demonstrate the efficacy of a 29 kDa β1,4‐galactose terminal glycoprotein ( GP 29) of L eishmania donovani ( LD ) in an in vitro macrophage model and an in vivo mouse model of VL . GP 29 induced splenic macrophages to release NO and ROS in appreciable amounts that resulted in effective parasite clearance from macrophages. This was associated with the toll‐like receptor ( TLR )‐4 mediated IL ‐12 induction and inhibition of TLR 2‐mediated IL ‐10 production. Two subcutaneous injections of GP 29 at fortnightly intervals resulted in dominant IL ‐12‐mediated IFN ‐γ production and 100% animals were protected against a subsequent challenge with virulent LD parasites. Vaccinated mice showed a reversal of T ‐cell anergy, significantly elevated expression of i NOS and a type‐1 I g G subclass response. Moreover, vaccinated mice downregulated arginase1 and IL ‐10 expression but did not alter IL ‐4 expression. The IFN ‐γ/ IL ‐10 ratio regulated the intensity of the protective immune response. Experiments with IFN ‐γ and IL ‐10 knockout mice reiterated the role IL ‐10 and IFN ‐γ play in disease progression or resolution in the murine model of VL .