Department of Biological Sciences, Mississippi State University, Starkville, MS, United States.
Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United States.
Front Cell Infect Microbiol. 2022 May 26;12:886901. doi: 10.3389/fcimb.2022.886901. eCollection 2022.
Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. and mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation of , , and . Enrichment of gene ontology groups differentially expressed in tissues were strongly correlated to IFN-β and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia.
细胞在感染部位的凋亡是关闭炎症信号、避免组织损伤和防止脓毒症进展的必要条件。使用磁珠面板分析，用 TIGR4 株肺炎球菌挑战 和 小鼠，并从肺部和血液中定量细胞因子。 小鼠表现出更高的肺部和血液中几种主要炎症细胞因子的水平，包括 IL-6、G-CSF、RANTES、IL-12、IFN-γ和 IP-10。 小鼠对细菌传播更敏感，体重减轻比其野生型对照更明显。对整个肺组织的 RNA 测序分析表明，Puma 依赖于 、 和 的调节。在 组织中差异表达的基因本体组富集与 IFN-β 和 -γ信号强烈相关。在这里，我们首次证明了 Puma 在细菌性肺炎期间禁止细胞因子风暴的作用。这些发现进一步表明，在肺部炎症期间靶向 IFN 信号的免疫调节具有作用。此外，我们的发现表明，在肺炎球菌性肺炎固有免疫反应的早期阶段，编码调节和结合蛋白的基因具有以前未证明的作用。
