Elimination of helminth infection restores HIV-1C vaccine-specific T cell responses independent of helminth-induced IL-10.
Elimination of helminth infection restores HIV-1C vaccine-specific T cell responses independent of helminth-induced IL-10.
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DOI：
10.1016/j.vaccine.2009.11.019
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发表时间：
2010-02-03
期刊：
影响因子：
5.5
通讯作者：
Harn, Donald A.
中科院分区：
文献类型：
--
作者：
Da'dara, Akram A.;Harn, Donald A.
艾滋病毒-1在发展中国家的流行率最高；同样，蠕虫寄生虫在这些地区往往高度流行。蠕虫是一种强大的免疫调节剂，对感染宿主针对HIV-1和其他病原体产生保护性疫苗特异性T细胞免疫反应的能力产生负面影响。事实上，之前我们发现感染曼氏血吸虫的小鼠显著损害了HIV-1C疫苗特异性T细胞反应。驱虫药是可用的，而且价格便宜；因此，在这项研究中，我们评估了在接种HIV-1C DNA疫苗之前消除血吸虫感染是否会增加接受者对疫苗的特异性反应。正如预期的那样，感染曼氏血吸虫的小鼠的脾细胞产生的白介素4和白介素10的量显著高于未感染的小鼠，而干扰素γ的量显著低于未感染的小鼠。在用吡喹酮(PZQ)治疗清除寄生虫后，尽管脾细胞产生的IL-10水平与感染小鼠的脾细胞相似或更高，但脾肿大明显减少。然而，我们发现，与未治疗的小鼠的脾细胞相比，PZQ治疗显著增加了对刀豆蛋白A或SEA反应的干扰素-γ水平。重要的是，在PZQ治疗后8周，PZQ治疗导致HIV-1C疫苗特异性T细胞反应完全恢复。在驱除寄生虫感染后，HIV-1C疫苗特异性T细胞反应的恢复是时间依赖的，但令人惊讶的是，它与寄生虫抗原诱导的IL-4和IL-10水平无关。我们的研究表明，在蠕虫流行的情况下，消除蠕虫提供了一种负担得起的简单方法，可以恢复对HIV-1和其他传染病的T细胞疫苗的免疫应答。
HIV-1 prevalence is highest in developing countries; similarly helminth parasites are often highly endemic in these same areas. Helminths are strong immune modulators, and negatively impact the ability of the infected hosts to mount protective vaccine specific T cell immune responses for HIV-1 and other pathogens. Indeed, previously we found that Schistosoma mansoni infected mice had significantly impaired HIV-1C vaccine specific T cell responses. Anthelminthics are available and inexpensive; therefore, in this study, we evaluated whether elimination of schistosome infection prior to vaccination with an HIV-1C DNA vaccine would increase recipients vaccine specific responses. As expected, splenocytes from S. mansoni infected mice produced significantly elevated amounts of interleukin (IL)-4 and IL-10, and significantly lower amounts of interferon (IFN)-γ than splenocytes from naïve mice. Following elimination of parasites by praziquantel (PZQ) treatment, splenomegaly was significantly reduced, though splenocytes produced similar or higher levels of IL-10 than splenocytes from infected mice. However, we found that PZQ treatment significantly increased levels of IFN-γ in response to Concanavalin A or SEA compared to splenocytes from untreated mice. Importantly, PZQ treatment resulted in complete restoration of HIV-1C vaccine specific T cell responses at 8 weeks post PZQ treatment. Restoration of HIV-1C vaccine specific T cell responses following elimination of helminth infection was time dependent, but surprisingly independent of the levels of IL-4 and IL-10 induced by parasite antigens. Our study shows that elimination of worms offers an affordable and a simple means to restore immune responsiveness to T cell based vaccines for HIV-1 and other infectious diseases in helminth endemic settings.
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