Investigating the immunological and life history consequences of early life adversity

研究早期生活逆境的免疫学和生活史后果

• 批准号: 1714730
• 负责人: India Schneider-Crease
• 金额: $ 13.8万
• 依托单位: Schneider-Crease India
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1714730&HistoricalAwards=false
• 关键词: Investigating; immunological; life; history; consequences

This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. This postdoctoral fellowship award supports a rising scholar in the investigation of how early life adversity triggers trade-offs in immunological development in a nonhuman primate model, the gelada. Trauma during infancy, the most vulnerable period of life, affects both immediate and long-term health. The negative consequences of adversity during early life may arise, in part, from tradeoffs that occur when limited resources are preferentially allocated to the most important developmental processes. One such tradeoff is thought to be between investment in the two primary components of the immune system: the innate and acquired immune responses. Innate immunity is thought to be energetically cheap relative to acquired immunity; thus, adversity in early life is expected to stimulate increased investment in innate immunity. The prioritization of innate immunity and the de-prioritization of acquired immunity may facilitate the immediate survival of infants exposed to early life adversity, but may also make these infants more vulnerable to certain diseases in adulthood. Understanding the link between early life adversity and immune development is thus central to endeavors to protect the health of vulnerable populations. Geladas are an exceptional model species for this investigation because some infants are exposed to early life adversity in the form of attacks from adult males during infanticide attempts. This research fills critical gaps in the current understanding of the mechanisms and evolution of human social experience and health, and thus provides information that is imperative to efforts to mediate the consequences of childhood adversity. Furthermore, this fellowship comes at an exciting time in the development of powerful tools in genomics and eco-immunology that can be applied in studies of wild populations. The funded research thus plays an important role in advancing the use of these techniques for research on both human and non-human animal populations.Early life adversity plays an essential role in shaping the trajectory of survival, health, and reproductive success in adulthood. The long-lasting consequences of early life adversity may be due to trade-offs between physiologically costly processes - often a zero-sum game in the face of limited resources. The two arms of the immune response are prime candidates for trade-offs given that immunity is both costly and necessary for survival, and such trade-offs are expected to affect the ability of organisms to effectively combat pathogens. Organisms may therefore react to adversity by prioritizing the development of one component of the immune system at the expense of another. The innate immune response, which acts as a generalized "first-responder" to pathogens, is hypothesized to carry lower costs than the acquired immune response, which acts in long-term pathogen recognition and combat. Cues of adversity are thus expected to stimulate increased investment in innate immunity relative to acquired immunity. The present research investigates the impact of early life adversity on immunological development in geladas. Two characteristics of geladas (Theropithecus gelada) make them an excellent system in which to examine how early life adversity affects immune activation and disease susceptibility: (1) A high percentage of infants experience early life adversity in the form of the threat of infanticide from new immigrant males, which should select for adaptive plasticity in infants that allows them to preferentially allocate energetic resources to enhance immediate survival; (2) Geladas are infected by two sets of pathogens, each of which triggers distinct immune activity. The present study addresses two questions in this system: (1) Are there tradeoffs between innate and acquired immunity for infants that experience early life adversity? and (2) What are the long-term consequences of immunological tradeoffs during development? This research takes an interdisciplinary approach to answering these questions, using novel tools in eco-immunology and genomics to non-invasively quantify immune activation and disease risk in geladas under long-term study in the wild. These health data will be paired with longitudinal life history data to evaluate the impact of adversity in early life on immunological development and adult health and fitness. By quantifying variation in components of health, immune function, and reproductive success in these geladas, this research examines the evolutionary basis of the physiological consequences of early life adversity.

该奖项是作为NSF的社会，行为和经济科学博士后研究奖学金（SPRF）计划的一部分提供的。SPRF计划的目标是为学术界，工业或私营部门和政府的科学事业准备有前途的早期职业博士级科学家。SPRF的奖励包括在知名科学家的赞助下进行两年的培训，并鼓励博士后研究员进行独立研究。NSF致力于促进来自科学界各部门的科学家，包括来自代表性不足的群体的科学家参与其研究计划和活动;博士后期间被认为是实现这一目标的专业发展的重要水平。每个博士后研究员必须解决推进各自学科领域的重要科学问题。这个博士后奖学金支持了一个正在崛起的学者在调查如何早期生活逆境触发权衡免疫发展在非人类灵长类动物模型，狮尾狒狒。婴儿期是生命中最脆弱的时期，其创伤会影响近期和长期健康。在生命早期，逆境的负面后果可能部分源于有限的资源优先分配给最重要的发展过程时发生的权衡。一个这样的权衡被认为是在免疫系统的两个主要组成部分：先天性和获得性免疫反应之间的投资。先天免疫被认为相对于后天免疫在能量上是便宜的;因此，生命早期的逆境预计会刺激对先天免疫的投资增加。先天免疫的优先地位和后天免疫的非优先地位可能有助于暴露于早期生活逆境的婴儿的立即存活，但也可能使这些婴儿在成年后更容易受到某些疾病的影响。因此，了解生命早期逆境与免疫发育之间的联系对于保护弱势群体健康的努力至关重要。狮尾狒狒是这项研究的一个特殊模式物种，因为一些婴儿在试图杀死成年雄性动物时会受到成年雄性动物的攻击。这项研究填补了目前对人类社会经验和健康的机制和演变的理解的关键空白，从而提供了对调解儿童逆境后果的努力至关重要的信息。此外，这项研究正值基因组学和生态免疫学领域开发可应用于野生种群研究的强大工具的激动人心的时刻。因此，受资助的研究在促进这些技术在人类和非人类动物种群研究中的应用方面发挥了重要作用。早期生活逆境在塑造成年期生存、健康和生殖成功的轨迹方面发挥着至关重要的作用。早期生活逆境的长期后果可能是由于生理上代价高昂的过程之间的权衡--在资源有限的情况下，这往往是一场零和游戏。免疫反应的两个分支是权衡的主要候选者，因为免疫既昂贵又是生存所必需的，这种权衡预计会影响生物体有效对抗病原体的能力。因此，生物体可能会通过优先发展免疫系统的一个组成部分而牺牲另一个组成部分来应对逆境。先天性免疫反应，作为一个广义的“第一反应者”病原体，被假设为进行成本低于获得性免疫反应，这在长期病原体识别和战斗。因此，相对于获得性免疫，逆境的线索预计会刺激先天免疫的投资增加。本研究探讨了生命早期逆境对狒狒免疫发育的影响。狮尾狒狒的两个特征（Theropithecus gelada）使它们成为一个很好的系统，可以研究早期生活逆境如何影响免疫激活和疾病易感性：（1）大部分婴儿在幼年时曾受到来自新移民男性的杀婴威胁，这应该选择适应性可塑性的婴儿，使他们能够优先分配能源，以提高即时生存;（2）狮尾狒狒被两种病原体感染，每种病原体都能引发不同的免疫活性。本研究解决了该系统中的两个问题：（1）对于经历早期生活逆境的婴儿来说，先天免疫和获得性免疫之间是否存在权衡？以及（2）在发育过程中免疫权衡的长期后果是什么？这项研究采用跨学科的方法来回答这些问题，使用生态免疫学和基因组学中的新工具，在野外长期研究中非侵入性地量化狒狒的免疫激活和疾病风险。这些健康数据将与纵向生活史数据配对，以评估早年逆境对免疫发育和成年健康和体能的影响。通过量化这些狒狒的健康，免疫功能和生殖成功的组成部分的变化，本研究探讨了生命早期逆境的生理后果的进化基础。

项目成果

Beyond infant death: the hidden costs of male immigration in geladas

除了婴儿死亡之外：狒狒中男性移民的隐性成本

• DOI: 10.1016/j.anbehav.2019.11.010
• 发表时间: 2020
• 期刊: Animal Behaviour
• 影响因子: 2.5
• 作者: Schneider-Crease, India;Chiou, Kenneth L.;Snyder-Mackler, Noah;Bergman, Thore J.;Beehner, Jacinta C.;Lu, Amy
• 通讯作者: Lu, Amy