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Pasteurella multocida (P. multocida) is a highly infectious, zoonotic pathogen. Outer membrane protein A (OmpA) is an important virulence component of the outer membrane of P. multocida. OmpA mediates bacterial biofilm formation, eukaryotic cell infection, and immunomodulation. It is unclear how OmpA affects the host immune response. We estimated the role of OmpA in the pathogenesis of P. multocida by investigating the effect of OmpA on the immune cell transcriptome. Changes in the transcriptome of rat alveolar macrophages (NR8383) upon overexpression of P. multocida OmpA were demonstrated. A model cell line for stable transcription of OmpA was constructed by infecting NR8383 cells with OmpA-expressing lentivirus. RNA was extracted from cells and sequenced on an Illumina HiSeq platform. Key gene analysis of genes in the RNA-seq dataset were performed using various bioinformatics methods, such as gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, and Protein–Protein Interaction Analysis. Our findings revealed 1340 differentially expressed genes. Immune-related pathways that were significantly altered in rat alveolar macrophages under the effect of OmpA included focal adhesion, extracellular matrix and vascular endothelial growth factor signaling pathways, antigen processing and presentation, nucleotide oligomerization domain-like receptor and Toll-like receptor signaling pathways, and cytokine-cytokine receptor interaction. The key genes screened were Vegfa , Igf2r , Fabp5 , P2rx1 , C5ar1 , Nedd4l , Gas6 , Cxcl1 , Pf4 , Pdgfb , Thbs1 , Col7a1 , Vwf , Ccl9 , and Arg1. Data of associated pathways and altered gene expression indicated that OmpA might cause the conversion of rat alveolar macrophages to M2-like. The related pathways and key genes can serve as a reference for OmpA of P. multitocida and host interaction mechanism studies. • P. multocida OmpA was transcriptionally overexpressed in rat alveolar macrophages. • Dysfunction and polarization of alveolar macrophages. • Significant functional changes in tissue repair, angiogenesis and immunosuppression were found in RNA-seq bioinformatics analysis. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen which can cause pneumonia, sepsis and infections of skin and soft tissue. The host mostly relies on innate immune responses to defend against the infection of A. baumannii. Currently, it has been confirmed that fibroblasts involved in innate immune responses. Therefore, to explore how bovine skin fibroblasts mediated immune responses to defend against A. baumannii infection, we analyzed the differential transcripts data of bovine skin fibroblasts infected with bovine A. baumannii by RNA-sequencing (RNA-seq). We found that there were 3014 differentially expressed genes (DEGs) at 14h with bovine A. baumannii infection, including 1940 up-regulated genes and 1074 down-regulated genes. Gene Ontology (GO) enrichment showed that ubiquitin protein ligase binding, IL-6 receptor complex, ERK1 and ERK2 cascade terms were mainly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that innate immune pathways were significantly enriched, such as TNF, IL-17, NLR, MAPK, NF-κB, endocytosis, apoptosis and HIF-1 signaling pathways. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that GO terms such as chemokine receptor binding and Th17 cell differentiation and KEGG pathways such as TLR and cytokine-cytokine receptor interaction pathways were up-regulated. In addition, CASP3 and JUN were the core functional genes of apoptosis, while IL-6 , ERBB2 , EGFR , CHUK and MAPK8 were the core functional genes of immunity by Protein-Protein Interaction (PPI) analysis. Our study provided an in-depth understanding of the molecular mechanisms of fibroblasts against A. baumannii infection. It also lays the foundation for the development of new therapeutic targets for the diseases caused by A. baumannii infection and formulates effective therapeutic strategies for the prevention and control of the diseases caused by A. baumannii. • Highly virulent A. baumannii conferred immune responses on fibroblasts at MOI = 30. • A large number of DEGs involved in innate immunity such as IL-6 , etc. • KEGG and GSEA enrichment showed that TLR, NLR, IL-17, TNF, endocytosis, apoptosis, MAPK signaling pathways were enriched. • CASP3 and JUN were the core genes of apoptosis, while IL-6 , ERBB2 , EGFR , CHUK and MAPK8 were the core genes of immunity. [ABSTRACT FROM AUTHOR]