There is growing evidence that prenatal immune activation contributes to neuropsychiatric disorders. Here, we show that early postnatal immune activation resulted in profound impairments in social behavior, including in social memory in adult male mice heterozygous for a gene responsible for tuberous sclerosis complex (Tsc2^+/−), a genetic disorder with high prevalence of autism. Early postnatal immune activation did not affect either wild-type or female Tsc2^+/− mice. We demonstrate that these memory deficits are caused by abnormal mammalian target of rapamycin–dependent interferon signaling and impairments in microglia function. By mining the medical records of more than 3 million children followed from birth, we show that the prevalence of hospitalizations due to infections in males (but not in females) is associated with future development of autism spectrum disorders (ASD). Together, our results suggest the importance of synergistic interactions between strong early postnatal immune activation and mutations associated with ASD.

中文翻译：

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出生后免疫激活导致结节性硬化症小鼠模型的社交缺陷：小胶质细胞的作用和临床意义


越来越多的证据表明，产前免疫激活会导致神经精神疾病。在这里，我们发现，出生后早期的免疫激活会导致社会行为的严重损害，包括结节性硬化症（ Tsc2 ^+/- ）基因杂合的成年雄性小鼠的社会记忆，结节性硬化症是一种自闭症患病率很高的遗传性疾病。出生后早期免疫激活不会影响野生型或雌性Tsc2 ^+/-小鼠。我们证明这些记忆缺陷是由雷帕霉素依赖性干扰素信号传导的哺乳动物靶标异常和小胶质细胞功能损伤引起的。通过挖掘超过 300 万儿童出生后的医疗记录，我们发现男性（而非女性）因感染而住院的患病率与自闭症谱系障碍 (ASD) 的未来发展相关。总之，我们的结果表明，强烈的产后早期免疫激活与 ASD 相关突变之间协同相互作用的重要性。