Tuberculosis is an infectious disease of increasing importance in humans and cattle, causing significant mortality, morbidity, and economic loss worldwide. The rise of multidrug resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) is of particular concern. Mycobacterium tuberculosis (the primary cause of human TB) and Mycobacterium bovis (the primary cause of bovine TB) are remarkably similar at the genome sequence level. In the face of this, it is important to understand the molecular mechanisms underpinning host responses to infection with these pathogens. This will have implications for diagnosis, vaccinology, and treatment of human TB and for disease control and management of bovine TB.
In the present study, differentially expressed genes (DEGs) within active functional modules (subnetworks) were analysed1. These DEGs were identified using RNA sequencing (RNA-seq) of human and bovine alveolar macrophages (hAM and bAM) 24 hours post infection (hpi) with M. tuberculosis and M. bovis, respectively. Following this, Ingenuityยฎ Pathway Analysis (IPAยฎ) was used to systematically extract enriched molecular pathways involved in host responses to infection2.
Table 1 shows an overview of some of the key findings in this study. The results were multifaceted and complex and encompassed many aspects of host-pathogen interactions, including pathogen recognition, cell signalling and downstream inflammatory processes. This study provides further evidence to help frame future research questions that will be vital to developing a complete understanding of host-pathogen interactions for pathogenic mycobacterial infections of humans and cattle.
Table 1: Top canonical pathways detected enriched for DEGs in bAM cells (infected with M. bovis) and hAM cells (infected with M. tuberculosis).
| Bovine alveolar macrophage | P-value | Human alveolar macrophage | P-value |
|---|---|---|---|
| Neuroinflammation Signalling Pathway | 3.66 ร 10-30 | Neuroinflammation Signalling Pathway | 7.36 ร 10-29 |
| Systemic Lupus Erythematosus In B Cell Signalling Pathway | 1.79 ร 10-28 | TH1 and TH2 Activation Pathway | 2.70 ร 10-28 |
| Role of Macrophages, Fibroblasts and Endothelial Cells In Rheumatoid Arthritis | 7.01 ร 10-27 | Granulocyte Adhesion and Diapedesis | 7.37 ร 10-28 |
| Hepatic Fibrosis Signalling Pathway | 5.98 ร 10-25 | Glucocorticoid Receptor Signalling | 3.26 ร 10-24 |
| Type I Diabetes Mellitus Signalling | 6.11 ร 10-25 | Agranulocyte Adhesion and Diapedesis | 4.01 ร 10-24 |
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