Macrophages Are Critical for Cross-Protective Immunity Conferred by Babesia microti against Babesia rodhaini Infection in Mice
Macrophages Are Critical for Cross-Protective Immunity Conferred by Babesia microti against Babesia rodhaini Infection in Mice
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DOI：
10.1128/iai.05900-11
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发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Xuan, Xuenan
中科院分区：
文献类型：
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作者：
Li, Yan;Terkawi, Mohamad Alaa;Xuan, Xuenan
虽然小鼠的微巴贝虫初次感染已被证明可以保护小鼠免受随后的罗德海巴贝虫的致命感染，但这种交叉保护背后的机制尚不清楚。为了揭示这一机制，我们研究了非致死性微螺旋体小鼠初次感染不同时间对随后致死性罗德海螺旋体感染结果的影响。同时感染这些寄生虫的小鼠导致寄生虫血症迅速增加，BALB/c小鼠死亡率为100%，与单独感染罗氏螺旋体的对照小鼠观察到的结果相同。相比之下，急性、缓解期和慢性期微螺旋体感染的小鼠完全不受罗德海螺旋体感染，导致低寄生虫率和无死亡率。用死亡的微氏贝氏体免疫小鼠，虽然诱导了高抗体反应，但不能保护小鼠免受罗德海贝氏体感染。有趣的是，受保护的小鼠在感染B. rodhaini后，抗体反应水平、细胞因子（包括γ干扰素[ifn - γ]、白细胞介素-2 [IL-2]、IL-8、IL-10和IL-12）和一氧化氮水平显著降低。慢性微螺旋体感染的SCID小鼠和ifn - γ缺陷小鼠表现出与免疫正常小鼠相当的保护反应。同样，在体内NK细胞的消耗并没有显著损害保护反应。相反，巨噬细胞消耗导致对B. rodhaini感染的易感性增加，这与它们的抗体和细胞因子谱的变化有关，表明巨噬细胞有助于抵抗这种感染。我们的结论是，未来巴贝斯虫疫苗的开发应该包括一种增强巨噬细胞适当激活的策略。
Although primary infection of mice with Babesia microti has been shown to protect mice against subsequent lethal infection by Babesia rodhaini, the mechanism behind the cross-protection is unknown. To unravel this mechanism, we investigated the influence of primary infection of mice with nonlethal B. microti using different time courses on the outcome of subsequent lethal B. rodhaini infection. Simultaneous infections of mice with these parasites resulted in rapid increases in parasitemia, with 100% mortality in BALB/c mice, as observed with control mice infected with B. rodhaini alone. In contrast, mice with acute, resolving, and chronic-phase B. microti infections were completely protected against B. rodhaini, resulting in low parasitemia and no mortalities. Mice immunized with dead B. microti were not protected from B. rodhaini infection, although high antibody responses were induced. Interestingly, the protected mice had significantly decreased levels of antibody response, cytokines (including gamma interferon [IFN-gamma], interleukin-2 [IL-2], IL-8, IL-10, and IL-12), and nitric oxide levels after infection with B. rodhaini. SCID mice and IFN-gamma-deficient mice with chronic B. microti infections demonstrated protective responses comparable to those of immunocompetent mice. Likewise, in vivo NK cell depletion did not significantly impair the protective responses. Conversely, macrophage depletion resulted in increased susceptibility to B. rodhaini infection associated with changes in their antibody and cytokines profiles, indicating that macrophages contribute to the protection against this challenge infection. We conclude that future development of vaccines against Babesia should include a strategy that enhances the appropriate activation of macrophages.