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

## TL;DR

This study explores how Mycobacterium orygis causes severe lung disease in cattle, identifying immune-related genes that could help detect tuberculosis in animals.

## Contribution

The study identifies 14 potential biomarkers for active TB in cattle through comparative transcriptomics and granuloma analysis.

## Key findings

- M. orygis causes severe lung lesions in cattle, including necrotic and cavitary granulomas.
- Transcriptomic analysis reveals dysregulated immune pathways and extracellular matrix remodeling in infected cattle.
- 14 key immunomodulators are proposed as potential biomarkers for bovine tuberculosis.

## 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.