Goldkamp Anna K, Atchison Randy G, Falkenberg Shollie M, Dassanayake Rohana P, Neill John D, Casas Eduardo
Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, Department of Agriculture, Ames, IA, USA.
Animal Plant Health Inspection Service, Department of Agriculture, Centers for Veterinary Biologics, Ames, IA, USA.
BMC Genomics. 2025 Apr 10;26(1):361. doi: 10.1186/s12864-025-11549-2.
Mycoplasma bovis is a prominent pathogen associated with respiratory disease in livestock. Respiratory disease in cattle often involves co-infection, where a primary viral infection can weaken the host immune system and thus enhance subsequent bacterial infection. The objective of this study was to investigate changes in the host (cattle) transcriptome during bacterial-viral co-infection. RNA sequencing was done in whole blood cells (WBC), liver, mesenteric lymph node (MLN), tracheal-bronchial lymph node (TBLN), spleen, and thymus collected from Control animals (n = 2), animals infected with M. bovis (MB; n = 3), and animals infected with M. bovis and bovine viral diarrhea virus (BVDV) (Dual; n = 3).
Thymus and spleen had the greatest number of differentially expressed genes (DEGs) out of all tissues analyzed. In spleen, genes involved in maintenance of the extracellular matrix (ECM) including collagen type XV alpha 1 chain (COL15A1), collagen type IV alpha 2 chain (COL4A2), and heparan sulfate proteoglycan 2 (HSPG2) were the most significantly downregulated in Dual compared to Control and MB. In thymus, complement 3 (C3) was a highly significant DEG and upregulated in Dual compared to Control and MB. Interferon alpha inducible protein 6 (IFI6) and interferon-induced transmembrane proteins (IFITM1 and IFITM3), were significantly associated with infection status and upregulated in spleen and thymus of Dual compared to Control and MB.
Downregulation of ECM components may cause degradation of the ECM and contribute to increased viral spread due to co-infection. Hyperactivation of complement pathway genes may contribute to damage to the thymus and influence severity of co-infection. Co-expression of IFI6, IFITM1 and IFITM3 across lymphoid tissues may be connected to enhanced pathogenesis in co-infection. These findings suggest co-infection exacerbates disease severity through modulation of ECM components in spleen and complement and coagulation cascades in the thymus. These impacted pathways may underlie thymic atrophy and impaired pathogen clearance due to BVDV and M. bovis co-infection.
牛支原体是家畜呼吸道疾病的一种主要病原体。牛的呼吸道疾病常涉及混合感染，原发性病毒感染可削弱宿主免疫系统，从而增强随后的细菌感染。本研究的目的是调查细菌 - 病毒混合感染期间宿主（牛）转录组的变化。对从对照动物（n = 2）、感染牛支原体的动物（MB；n = 3）以及感染牛支原体和牛病毒性腹泻病毒（BVDV）的动物（双重感染；n = 3）采集的全血细胞（WBC）、肝脏、肠系膜淋巴结（MLN）、气管 - 支气管淋巴结（TBLN）、脾脏和胸腺进行了RNA测序。
在所分析的所有组织中，胸腺和脾脏中差异表达基因（DEG）的数量最多。在脾脏中，与细胞外基质（ECM）维持相关的基因，包括XV型胶原α1链（COL15A1）、IV型胶原α2链（COL4A2）和硫酸乙酰肝素蛋白聚糖2（HSPG2），与对照和MB相比，在双重感染组中下调最为显著。在胸腺中，补体3（C3）差异极为显著，与对照和MB相比，在双重感染组中上调。干扰素α诱导蛋白6（IFI6）以及干扰素诱导跨膜蛋白（IFITM1和IFITM3）与感染状态显著相关，与对照和MB相比，在双重感染组的脾脏和胸腺中上调。
ECM成分的下调可能导致ECM降解，并因混合感染而导致病毒传播增加。补体途径基因的过度激活可能导致胸腺损伤，并影响混合感染的严重程度。IFI6、IFITM1和IFITM3在淋巴组织中的共表达可能与混合感染中增强的发病机制有关。这些发现表明，混合感染通过调节脾脏中的ECM成分以及胸腺中的补体和凝血级联反应加剧了疾病的严重程度。这些受影响的途径可能是BVDV和牛支原体混合感染导致胸腺萎缩和病原体清除受损的基础。
