Early CD44(hi)CD4(+) and CD44(hi)CD8(+) T cell numbers and the absence of mannose-rich glycoconjugates determine the protective outcome of anti-leishmanial immunity
- Author(s)
- Kedzierski, L; Curtis, JM; Kedzierska, K;
- Details
- Publication Year 2009-07,Volume 136,Issue #8,Page 833-840
- Journal Title
- PARASITOLOGY
- Publication Type
- Journal Article
- Abstract
- Vaccination remains the best hope for control of all forms Of leishmaniasis, and the development of a safe and effectively vaccine is a critical global public-health priority. Our previous work showed that immunization with non-persistent phosphomannomutase-deficient (Delta PMM) 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 Delta PMM L. major parasites With human PMM2 to determine whether We could further improve the protection. Complemented Delta PMM 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 Delta PMM-vaccinated mice. However, the numbers of the activated CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells recruited to the draining lymph nodes early after Leishmania infection 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 outcomes of anti-leishmanial immunity
- Publisher
- CAMBRIDGE UNIV PRESS
- Keywords
- LEISHMANIA-MEXICANA PHOSPHOMANNOMUTASE; RECONSTITUTED NUDE-MICE; CUTANEOUS LEISHMANIASIS; INFECTED MACROPHAGES; LIPOPHOSPHOGLYCAN; VACCINATION; VIRULENCE; PARASITES; DISEASE; TROPICA
- Publisher's Version
- https://doi.org/10.1017/S031182009006301
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-07-01 12:00:00