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Early CD44hiCD4+ and CD44hiCD8+ T cell numbers and the absence of mannose-rich glycoconjugates determine the protective outcome of anti-leishmanial immunity

Published online by Cambridge University Press:  02 June 2009

L. KEDZIERSKI ,
J. M. CURTIS  and
K. KEDZIERSKA
L. KEDZIERSKI*
Affiliation:
Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
J. M. CURTIS
Affiliation:
Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
K. KEDZIERSKA
Affiliation:
Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia
*
*Corresponding author: Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville3052, Australia. Tel: +61 3 93452475. Fax +61 3 93450852. E-mail: [email protected]
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Summary

Vaccination remains the best hope for control of all forms of leishmaniasis, and the development of a safe and effective vaccine is a critical global public-health priority. Our previous work showed that immunization with non-persistent phosphomannomutase-deficient (ΔPMM) Leishmania major parasites confers significant protection in susceptible BALB/c mice due to increased T-cell numbers and suppression of IL-10 and IL-13 early during infection. Here, we complemented the ΔPMM L. major parasites with human PMM2 to determine whether we could further improve the protection. Complemented ΔPMM parasites have restored glycoconjugate biosynthesis, while retaining avirulence of the parental knockout strain. Immunization with hPMM2 add-back parasites showed similar Th1/Th2 cytokine profiles to that observed in ΔPMM-vaccinated mice. However, the numbers of the activated CD4+CD44hi and CD8+CD44hi T cells recruited to the draining lymph nodes early after Leishmania infection were reduced, leading to decreased protection following hPMM2-immunization. Thus, the magnitude of T-cell responses early in the infection and the absence of mannose-rich glycoconjugates determine the protective outcome of anti-leishmanial immunity.

Keywords

Leishmaniavaccinephosphomannomutaseglycoconjugate
Type
Research Article
Information
Parasitology , Volume 136 , Issue 8 , July 2009 , pp. 833 - 840
Copyright
Copyright © Cambridge University Press 2009

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