Uninfected mosquito bites confer protection against infection with malaria parasites
Uninfected mosquito bites confer protection against infection with malaria parasites
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DOI：
10.1128/iai.01928-06
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
McDowell, Mary Ann
中科院分区：
文献类型：
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作者：
Donovan, Michael J.;Messmore, Andrew S.;McDowell, Mary Ann
尽管进行了数十年的研究和多项举措，但疟疾仍然是世界上最严重的传染病之一。疟疾控制和疫苗开发的新见解对于阻止这种疾病在全球范围内的惊人影响至关重要（A。Bjorkman和A. Bhattarai，Acta Trop.94：163-169，2005）;最终成功的疫苗策略无疑将是多因素的，包括多种抗原并靶向疟原虫生物学的不同方面（M. F. Good等人，Immunol.Rev.201：254-267，2004）。使用小鼠模型的疟疾感染，我们在这里表明，暴露于叮咬未感染的蚊子感染约氏疟原虫之前，影响局部和全身免疫反应，并限制寄生虫的发展在主机内。在主机预先暴露于未感染的蚊子叮咬，减少寄生虫的负担在肝脏中检测到早期，并在血液阶段的生命周期中，这些负担仍然低于那些在主机接收蚊子叮咬只在感染时。反复暴露于未感染蚊子的叮咬会使免疫应答向辅助性T细胞1（Th 1）表型倾斜，如白细胞介素-12、γ干扰素和诱导型一氧化氮合酶水平升高所示。这些数据表明，除了蚊子唾液成分的抗疟疾疫苗可能是一个可行的策略，创造一个Th 1偏置的环境，已知是有效的抗疟疾感染。此外，这种策略对于开发疫苗以对抗其他蚊子传播的病原体可能很重要。
Despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. New insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease (A. Bjorkman and A. Bhattarai, Acta Trop. 94:163-169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites' biology (M. F. Good et al., Immunol. Rev. 201:254-267, 2004). Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to Plasmodium yoelii infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquito-transmitted pathogens.