Sun Ruoyuan, Yu Jinxi, Zou Zeyang, Yang Shuaini, Tuo Yuqing, Tan Lu, Zhang Hong, Sun Longhao, Bai Hong
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China.
Department of General Surgery, Tianjin Medial University General Hospital, Tianjin 300052, China.
Int Immunopharmacol. 2025 Feb 6;147:113943. doi: 10.1016/j.intimp.2024.113943. Epub 2025 Jan 2.
FcγRI, a pivotal cell surface receptor, is implicated in diverse immune responses and is ubiquitously expressed on numerous immune cells. However, its role in intracellular bacterial infections remains understudied.
Wild-type (WT) and FcγRI knockout (FcγRI-KO) mice were inoculated intranasally with a specific dose of C. muridarum. Lung tissues were harvested for transcriptome sequencing, and flow cytometry was employed to validate bioinformatics immune infiltration analysis. Differentially expressed DC-associated genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to elucidate their functions during infection. A PPI network was constructed to pinpoint crucial genes, and qPCR was utilized to confirm their expression changes. Additionally, we compared body weight, lung Chlamydia load, and pathological alterations between WT and FcγRI-KO mice post-infection to assess the effect of FcγRI on inflammation via gene regulation. Lastly, an mRNA-miRNA-lncRNA network was formulated to further probe the molecular mechanisms of FcγRI in C. muridarum infection.
Post-C. muridarum infection, FcγRI-KO mice exhibited a notable decrease in DC infiltration and maturation, along with downregulated co-stimulatory molecules (CD40, CD80, CD86) in lung tissues. Differential gene analysis identified 26 differentially expressed DC-related genes implicated in DC proliferation, migration, and inflammatory responses. KEGG analysis revealed their close association with key immune pathways. The PPI network delineated two modules, with the top six genes in the pivotal cluster 1 (Ccl4, Il6, Ccl3, Ptgs2, Il 1α, Il7) being significantly downregulated in FcγRI-KO mice. A ceRNA network encompassing 12 miRNAs and 37 lncRNAs regulating four key genes (Ptgs2, Il1α, Il6, Il7) was also constructed.
In C. muridarum respiratory infections, FcγRI facilitates DC infiltration and maturation, upregulates six pro-inflammatory genes (Ccl4, Il6, Ccl3, Ptgs2, Il1α, Il7), and exhibits a pro-inflammatory role. A key ceRNA network was formulated to unravel the underlying molecular mechanisms.
FcγRI是一种关键的细胞表面受体，参与多种免疫反应，在众多免疫细胞上普遍表达。然而，其在细胞内细菌感染中的作用仍研究不足。
将野生型（WT）和FcγRI基因敲除（FcγRI-KO）小鼠经鼻接种特定剂量的鼠衣原体。采集肺组织进行转录组测序，并采用流式细胞术验证生物信息学免疫浸润分析。对差异表达的DC相关基因进行基因本体论和京都基因与基因组百科全书分析，以阐明其在感染过程中的功能。构建蛋白质-蛋白质相互作用（PPI）网络以确定关键基因，并利用qPCR确认其表达变化。此外，我们比较了WT和FcγRI-KO小鼠感染后体重、肺衣原体载量和病理改变，以评估FcγRI通过基因调控对炎症的影响。最后，构建了一个mRNA- miRNA- lncRNA网络，以进一步探究FcγRI在鼠衣原体感染中的分子机制。
鼠衣原体感染后，FcγRI-KO小鼠的DC浸润和成熟显著减少，肺组织中共刺激分子（CD40、CD80、CD86）下调。差异基因分析确定了26个与DC增殖、迁移和炎症反应相关的差异表达DC相关基因。KEGG分析揭示了它们与关键免疫途径的密切关联。PPI网络划分出两个模块，关键簇1中的前六个基因（Ccl4、Il6、Ccl3、Ptgs2、Il1α、Il7）在FcγRI-KO小鼠中显著下调。还构建了一个包含12个miRNA和37个lncRNA的ceRNA网络，这些miRNA和lncRNA调节四个关键基因（Ptgs2、Il1α、Il6、Il7）。
在鼠衣原体呼吸道感染中，FcγRI促进DC浸润和成熟，上调六个促炎基因（Ccl4、Il6、Ccl3、Ptgs2、Il1α、Il7），并发挥促炎作用。构建了一个关键的ceRNA网络以揭示潜在的分子机制。
