FcγRI plays a pro-inflammatory role in the immune response to Chlamydia respiratory infection by upregulating dendritic cell-related genes

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.