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首页> 外文期刊>Parasitology >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.
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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.

机译：早期的CD44（hi）CD4 +和CD44（hi）CD8 + T细胞数量以及缺乏富含甘露糖的糖缀合物决定了抗利什曼免疫的保护性结果。

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摘要

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 (DeltaPMM) 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 DeltaPMM L. major parasites with human PMM2 to determine whether we could further improve the protection. Complemented DeltaPMM 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 DeltaPMM-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 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.
机译：接种疫苗仍然是控制所有形式的利什曼病的最大希望，开发安全有效的疫苗是全球公共卫生的重中之重。我们以前的工作表明，由于感染过程中T细胞数量增加以及IL-10和IL-13的抑制，非持久性磷酸甘露糖酶缺乏症（DeltaPMM）利什曼原虫主要寄生虫的免疫作用为易感BALB / c小鼠提供了重要的保护。在这里，我们用人类PMM2补充了DeltaPMM L.主要寄生虫，以确定我们是否可以进一步提高保护水平。互补的DeltaPMM寄生虫恢复了糖缀合物的生物合成，同时保留了亲本敲除菌株的无毒力。用hPMM2添加寄生虫进行的免疫接种显示与在DeltaPMM疫苗接种的小鼠中观察到的Th1 / Th2细胞因子相似。然而，在利什曼原虫感染后早期募集到引流淋巴结的活化的CD4 + CD44（hi）和CD8 + CD44（hi）T细胞数量减少，导致hPMM2免疫后的保护作用降低。因此，在感染早期的T细胞应答的强度和富含甘露糖的糖缀合物的缺乏决定了抗利什曼病毒免疫的保护结果。

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