Transcriptomic insights into Mycobacterium orygis infection-associated pulmonary granulomas reveal multicellular immune networks and tuberculosis biomarkers in cattle.

IF 7.9 2区 农林科学 Q1 VETERINARY SCIENCES
Veterinary Quarterly Pub Date : 2025-12-01 Epub Date: 2025-05-27 DOI:10.1080/01652176.2025.2509503
Rishi Kumar, Sripratyusha Gandham, Vinay Bhaskar, Manas Ranjan Praharaj, Hemanta Kumar Maity, Uttam Sarkar, Bappaditya Dey
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引用次数: 0

Abstract

Mycobacterium orygis, a member of the Mycobacterium tuberculosis complex (MTBC), has emerged as a significant contributor to tuberculosis (TB) in cattle, wildlife, and humans. However, understanding about its pathogenesis and severity is limited, compounded by the lack of reliable TB biomarkers in cattle. This study delves into the comparative pathology and transcriptomic landscape of pulmonary granulomas in cattle naturally infected with M. orygis, using high-throughput RNA sequencing. Histopathological analysis revealed extensive, multistage granulomatous, necrotic, and cavitary lesions, indicative of severe lung pathology induced by M. orygis. Transcriptomic profiling highlighted numerous differentially expressed genes and dysregulated pathways related to immune response modulation and extracellular matrix remodelling. Additionally, cell type enrichment analysis provided insights into the multicellularity of the granulomatous niche, emphasising complex cell-cell interactions within TB granulomas. Via comparative transcriptomics leveraging publicly available bovine and human TB omics datasets, 14 key immunomodulators (SOD2, IL1α/β, IL15, IL18, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL8/MCP-2, CCL20/MIP-3α, CXCL2/MIP-2, CXCL10/IP-10, CXCL11, and IFN-γ) were identified as potential biomarkers for active TB in cattle. These findings significantly advance our understanding of M. orygis pathogenesis in bovine TB and highlight potential targets for the development of diagnostic tools for managing and controlling the disease.

转录组学对牛羊分枝杆菌感染相关的肺肉芽肿揭示了多细胞免疫网络和结核病生物标志物。
水稻分枝杆菌是结核分枝杆菌复合体(MTBC)的一员,已成为牛、野生动物和人类结核病(TB)的重要贡献者。然而,对其发病机制和严重程度的了解是有限的,再加上在牛中缺乏可靠的结核病生物标志物。本研究利用高通量RNA测序技术,深入研究了自然感染稻瘟杆菌的牛肺肉芽肿的比较病理学和转录组学景观。组织病理学分析显示广泛,多期肉芽肿,坏死和空洞病变,表明严重的肺病理由稻瘟杆菌引起。转录组学分析强调了与免疫反应调节和细胞外基质重塑相关的许多差异表达基因和失调途径。此外,细胞类型富集分析提供了对肉芽肿生态位的多细胞性的见解,强调了结核肉芽肿中复杂的细胞-细胞相互作用。利用公开的牛和人结核病组学数据集,通过比较转录组学,确定了14种关键免疫调节剂(SOD2、il -1α /β、il - 15、il - 18、CCL2/MCP-1、CCL3/MIP-1α、CCL4/MIP-1β、CCL8/MCP-2、CCL20/MIP-3α、CXCL2/MIP-2、CXCL10/IP-10、CXCL11和IFN-γ)作为牛活活性结核病的潜在生物标志物。这些发现极大地促进了我们对牛结核分枝杆菌发病机制的理解,并突出了开发管理和控制该疾病的诊断工具的潜在目标。
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来源期刊
Veterinary Quarterly
Veterinary Quarterly VETERINARY SCIENCES-
CiteScore
13.10
自引率
1.60%
发文量
18
审稿时长
>24 weeks
期刊介绍: Veterinary Quarterly is an international open access journal which publishes high quality review articles and original research in the field of veterinary science and animal diseases. The journal publishes research on a range of different animal species and topics including: - Economically important species such as domesticated and non-domesticated farm animals, including avian and poultry diseases; - Companion animals (dogs, cats, horses, pocket pets and exotics); - Wildlife species; - Infectious diseases; - Diagnosis; - Treatment including pharmacology and vaccination
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