Mycobacterial Infections and Host Immune Responses in Ruminant Systems

Mycobacterial pathogens such as Mycobacterium avium subspecies paratuberculosis (MAP) and Mycobacterium bovis inflict chronic, often insidious diseases in domestic and wild ruminants, with substantial economic, animal-welfare and potential zoonotic implications. Infection typically follows oral or respiratory exposure, leading to pathogen uptake by intestinal or pulmonary macrophages. Early innate responses involve antimycobacterial macrophage activation and the recruitment of neutrophils and dendritic cells, but effective control hinges on the development of a robust cell-mediated immunity. A Th1-polarised response, orchestrated by interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α), promotes macrophage bactericidal mechanisms and granuloma formation, encapsulating infected cells. However, many mycobacterial species have evolved sophisticated strategies to subvert phagosome maturation, modulate antigen presentation and dampen pro-inflammatory signalling, resulting in persistent infection, intermittent pathogen shedding and progressive tissue pathology. Adaptive immunity in ruminants exhibits hallmarks of both protective and pathological processes, including the emergence of Th17-associated cytokines and regulatory T-cell networks that may restrain immunopathology at the expense of full pathogen clearance. Diagnostic and control measures remain challenged by long incubation periods, subclinical carriers and imperfect vaccines that interfere with diagnostic assays. Recent advances in molecular genetics, immunodiagnostics and novel spectroscopic approaches are beginning to refine our understanding of host–pathogen dynamics, offering new avenues for early detection, vaccine design and targeted immunomodulation.

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Mycobacterial Infections and Host Immune Responses in Ruminant Systems publication trend

The graph below shows the total number of articles in mycobacterial infections and host immune responses in ruminant systems across all publications each year (not limited to Nature Index journals).

Technical terms

Granuloma: Organized aggregate of macrophages, epithelioid cells and lymphocytes that walls off persistent pathogens.

Th1 response: Subset of CD4+ T helper cells producing IFN-γ and TNF-α to activate macrophages for intracellular pathogen clearance.

IFN-γ (Interferon-gamma): Cytokine central to macrophage activation and enhancement of antigen presentation in cell-mediated immunity.

Paratuberculosis (Johne’s disease): Chronic granulomatous enteritis in ruminants caused by MAP, characterised by weight loss and diarrhoea.

Aquaphotomics: Spectroscopic technique that examines water-molecule absorbance patterns to infer biochemical changes in biological fluids.

Alternative splicing: Post-transcriptional process by which exons are differentially joined to generate multiple mRNA isoforms from a single gene.

References

1. Alternative splicing of pre-mRNA modulates the immune response in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis. Frontiers in Immunology (2024).
2. A novel diagnostic approach to Paratuberculosis in dairy cattle using near-infrared spectroscopy and aquaphotomics. Frontiers in Cellular and Infection Microbiology (2024).
3. Pathogenesis, Molecular Genetics, and Genomics of Mycobacterium avium subsp. paratuberculosis, the Etiologic Agent of Johne’s Disease. Frontiers in Veterinary Science (2017).
4. From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. paratuberculosis. Veterinary Research (2014).
5. Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle. Veterinary Research (2015).
6. Control of paratuberculosis: who, why and how. A review of 48 countries. BMC Veterinary Research (2019).
7. The zoonotic potential of Mycobacterium avium ssp. paratuberculosis: a systematic review and meta-analyses of the evidence. Epidemiology and Infection (2015).