(1) Background: Pasteurellosis is a global zoonotic bacterial disease, which has caused significant economic impacts in animal husbandry. Nevertheless, there is limited understanding of the immune response between goat peripheral blood lymphocytes (PBLs) and goat-derived Pasteurella multocida (P. multocida). (2) Methods: To investigate the immune response of host PBLs during infection with P. multocida type D, we established an in vitro cell model utilizing isolated primary goat PBLs. Utilizing this in vitro infection model, we employed an enzyme-linked immunosorbent assay (ELISA) to assess the cytokine profile variation in goat PBLs following infection. Meanwhile, RNA sequencing and quantitative PCR (qPCR) methods were employed to analyze the gene expression profile. (3) Results: The ELISA test results indicated that the expression levels of pro-inflammatory cytokines, such as IL-6, IFN-γ, CXCL10, and IL-17A, were significantly elevated within 12 h after infection with P. multocida. In contrast, the levels of the anti-inflammatory cytokine IL-10 were found to be reduced. RNA sequencing and functional enrichment analysis identified 2114 differentially expressed genes (DEGs) that were primarily associated with cytokine-cytokine receptor interactions, viral protein-cytokine interactions, and the IL-17 signaling pathway. Furthermore, protein-protein interaction (PPI) network analysis and qPCR highlighted CD86, CCL5, CD8A, CXCL8, CTLA4, TNF, CD274, IL-10, IL-6, CXCL10, IFNG, and IL-17A that were crucial for the response of PBLs to P. multocida infection. (4) Conclusions: This study systematically revealed the characteristics of PBLs in goats following infection with goat-derived P. multocida type D through the analysis of cytokines and gene expression, providing important theoretical insights for a deeper understanding of the defense mechanisms in goats against P. multocida.

Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc–host interactions.