Innate immune memory provides antigen-independent cross-protection against heterologous pathogens. In Immunity, Lercher et al. determine the effects of innate immune memory in airway-resident immune cells on disease outcome of a second heterologous viral infection. The authors use a mouse-adapted SARS-CoV-2 strain for a murine infection model of SARS-CoV-2 recovery. They investigate the epigenetic and transcriptomics changes in airway-resident cells by single-nuclei combined assay of transposase-accessible chromatin with sequencing (snATAC-seq)/RNA sequencing (snRNA-seq) and find that alveolar macrophages present epigenetic imprinting after SARS-CoV-2 infection. Human monocytes from individuals after SARS-CoV-2 infection also retained epigenetic programs. Using an ex vivo culture of mouse primary airway-resident macrophages stimulated with different pattern recognition receptor agonists the authors show that the epigenetic imprinting associated with previous SARS-CoV-2 infection results in antiviral innate immune memory. The authors challenged mice that had recovered from SARS-CoV-2 with influenza A virus and observed milder pathology. Similar results were obtained after transferring airway-resident macrophages isolated from recovered mice into T cell-depleted naive recipient mice. Past SARS-CoV-2 infection ameliorates the pathology associated with secondary influenza A virus infection.

Original reference: Immunity https://doi.org/10.1016/j.immuni.2024.08.018 (2024)

先天免疫记忆提供针对异源病原体的抗原非依赖叉保护。在免疫学中，Lercher 等人确定了气道驻留免疫细胞中的先天免疫记忆对第二次异源病毒感染的疾病结果的影响。作者使用小鼠适应的 SARS-CoV-2 毒株进行 SARS-CoV-2 恢复的小鼠感染模型。他们通过转座酶可及染色质的单核联合测定与测序 （snATAC-seq）/RNA 测序 （snRNA-seq） 研究了气道驻留细胞的表观遗传学和转录组学变化，发现肺泡巨噬细胞在 SARS-CoV-2 感染后呈现表观遗传印记。SARS-CoV-2 感染后个体的人类单核细胞也保留了表观遗传程序。使用用不同模式识别受体激动剂刺激的小鼠原代气道驻留巨噬细胞的离体培养，作者表明，与先前 SARS-CoV-2 感染相关的表观遗传印记导致抗病毒先天免疫记忆。作者对从 SARS-CoV-2 中感染甲型流感病毒的小鼠进行攻击，并观察到较轻的病理。将从回收小鼠中分离的气道驻留巨噬细胞转移到 T 细胞耗尽的幼稚受体小鼠中后，也获得了类似的结果。过去的 SARS-CoV-2 感染改善了与继发性甲型流感病毒感染相关的病理。

原来参考：免疫 https://doi.org/10.1016/j.immuni.2024.08.018 （2024）