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Physiological age versus chronological age: defining how temperature impacts the aging of the mosquito immune system

生理年龄与实际年龄：定义温度如何影响蚊子免疫系统的老化

基本信息

批准号：
1936843
负责人：
Julian Hillyer
金额：
$ 89.59万
依托单位：
Vanderbilt University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1936843&HistoricalAwards=false
关键词：
Physiological age versus chronological defining

项目摘要

Insects fight infection by mounting immune responses. The effectiveness of these immune responses is dependent on multiple factors. One of these is the temperature of the environment, with different types of immune responses being stronger at different temperatures. Another factor that affects the strength of an insect’s immune response is age. As an insect becomes older, its immune system weakens. Although this is accepted, an important question that remains unanswered is whether the effect that temperature has on the immune system changes – for better or worse – as an insect becomes older. Therefore, the goal of this project is to understand how the immune systems ages, and the role that temperature plays in the aging process. This research is important because ongoing changes in the environment are shifting the temperature in which insects live. Overall, this project’s findings will allow researchers to predict how changes in environmental temperature alter the ability of an insect to fight an infection throughout its entire life, which is significant because some insects are essential for our food supply, and others are agricultural pests and transmitters of disease. Conducting this project will also advance the education of undergraduate students, graduate students and school-aged children, with the goal of motivating them to pursue experiences and careers in science. Outreach with high school students will be accomplished in partnership with the School for Science and Math at Vanderbilt, and outreach with elementary school students will be accomplished in partnership with Metro Nashville Public Schools.The ability of an insect to fight infection is modified by both the external environment and its life history. Two modifiers of immune processes are temperature and age. That is, immune proficiency changes as a function of the environmental temperature, and also declines as a function of age, a phenomenon known as senescence. Although both temperature and age impact immune proficiency, these two factors have always been studied in isolation. That is, studies testing the effect of temperature on immune function have been carried out at a predetermined age, and studies testing the effect of aging on immune proficiency have been carried out at a predetermined temperature. Therefore, the overarching goal of this project is to define how environmental temperature modifies immune senescence. Focusing on the societally important mosquito, Anopheles gambiae, this project will (i) define the infection-induced effects of temperature on the aging process, (ii) determine how temperature and infection interact to shape age-dependent humoral and cellular immunity, and (iii) define how blood feeding impacts the effect of temperature on aging. When completed, this project will uncover whether differences in environmental temperature alter the rate in which the insect immune system ages, resulting in a decoupling of chronological age and physiological age. The findings will provide a more holistic understanding of how insects fight infection in a changing landscape and should augment the robustness of models used to predict the effectiveness of insects as pollinators, agricultural pests, and disease vectors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

昆虫通过增强免疫反应来对抗感染。这些免疫反应的有效性取决于多种因素。其中之一是环境温度，不同类型的免疫反应在不同温度下更强。影响昆虫免疫反应强度的另一个因素是年龄。随着昆虫年龄的增长，其免疫系统会减弱。尽管这一点已被接受，但一个尚未得到解答的重要问题是，随着昆虫变老，温度对免疫系统的影响是否会发生变化（无论好坏）。因此，该项目的目标是了解免疫系统如何衰老，以及温度在衰老过程中所扮演的角色。这项研究很重要，因为环境的持续变化正在改变昆虫生存的温度。总体而言，该项目的研究结果将使研究人员能够预测环境温度的变化如何改变昆虫在其一生中抵抗感染的能力，这很重要，因为有些昆虫对我们的食物供应至关重要，而另一些昆虫则是农业害虫和疾病传播者。开展该项目还将促进本科生、研究生和学龄儿童的教育，目标是激励他们追求科学经验和职业生涯。对高中生的宣传将与范德比尔特科学与数学学院合作完成，对小学生的宣传将与纳什维尔都会公立学校合作完成。昆虫抵抗感染的能力会受到外部环境及其生活史的影响。免疫过程的两个调节因素是温度和年龄。也就是说，免疫能力随着环境温度的变化而变化，并且随着年龄的变化而下降，这种现象称为衰老。尽管温度和年龄都会影响免疫能力，但这两个因素一直是单独研究的。即，在预定的年龄下进行了测试温度对免疫功能的影响的研究，并且在预定的温度下进行了测试衰老对免疫能力的影响的研究。因此，该项目的首要目标是确定环境温度如何改变免疫衰老。该项目以对社会重要的蚊子冈比亚按蚊为重点，将 (i) 确定感染引起的温度对衰老过程的影响，(ii) 确定温度和感染如何相互作用以形成年龄依赖性体液和细胞免疫，以及 (iii) 确定吸血如何影响温度对衰老的影响。完成后，该项目将揭示环境温度的差异是否会改变昆虫免疫系统的衰老速度，从而导致实际年龄和生理年龄脱钩。这些发现将提供对昆虫如何在不断变化的景观中抵抗感染的更全面的了解，并应增强用于预测昆虫作为传粉媒介、农业害虫和疾病媒介的有效性的模型的稳健性。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。