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Vaccination Route That Induces Transforming Growth Factor � Production Fails To Elicit Protective Immunity against Leishmania donovani Infection

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Title Vaccination Route That Induces Transforming Growth Factor
� Production Fails To Elicit Protective Immunity against
Leishmania donovani Infection
 
Creator Bhowmick, Sudipta
Mazumdar, Tuhina
Ali, Nahid
 
Subject Infectious Diseases and Immunology
 
Description BALB/c mice immunized intraperitoneally (i.p.) and intravenously (i.v.) with Leishmania donovani promastigote
membrane antigens (LAg), either free or encapsulated in liposomes, were protected against challenge
infection with L. donovani, whereas mice immunized by the subcutaneous (s.c.) and intramuscular routes were
not protected. Protected mice showed strong parasite resistance in both the liver and spleen, along with
enhanced immunoglobulin G2a and delayed-type hypersensitivity responses. Again, mice vaccinated through
the i.p. and i.v. routes showed high levels of NO production after challenge infection. s.c. vaccination resulted
in an increased capacity of the spleen cells to produce prechallenge transforming growth factor � (TGF-�)
levels during the in vitro antigen recall response, whereas i.p. immunization induced production of prechallenge
gamma interferon, interleukin-12 (IL-12), and IL-4 levels, with a Th1 bias. Exposure to antigenstimulated
splenocyte supernatants of i.p. but not s.c. immunized mice activated macrophages for in vitro
parasite killing. As an enhanced level of TGF-� was detected in supernatants from unprotected s.c. immunized
mice, neutralization by anti-TGF-� antibody enhanced in vitro macrophage killing activity. The suppressive
role of this cytokine was evaluated in vivo by vaccination with liposomal LAg and anti-TGF-� antibody. Upon
parasite challenge, these animals showed significant protection in both the liver and spleen. Moreover, the
addition of recombinant TGF-� in splenocyte supernatants of i.p. immunized mice in vitro as well as in vivo
inhibited the protective ability of the macrophages by the i.p. route. Thus, the induction of high prechallenge
TGF-� limits the efficacy of vaccination by routes that are nonprotective.
 
Publisher American Society for Microbiology
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/191/1/INFECTION_AND_IMMUNITY%2C77(_4)%2C1514%2D1523%2C2009[81].pdf
Bhowmick, Sudipta and Mazumdar, Tuhina and Ali, Nahid (2009) Vaccination Route That Induces Transforming Growth Factor � Production Fails To Elicit Protective Immunity against Leishmania donovani Infection. Infection and Immunity, 77 (4). pp. 1514-1523.
 
Relation http://dx.doi.org/10.1128/IAI.01739-07
http://www.eprints.iicb.res.in/191/