Roadmap for the development of diagnostic test for bTB

What are we trying to achieve and why? What is the problem we are trying to solve?

To characterise the cell-mediated immune response during infection to identify which cytokines and other biomarkers
(transcriptomics, metabolomics… ) responses could be used to detect and monitor infection.

What are the scientific and technological challenges
(knowledge gaps needing to be addressed)?

• Investigating the specific roles and functional diversity of different T cell subsets, such as CD4+ T cells, CD8+ T cells, and gamma-delta T cells, during bTB infection.
• Understand how innate immune cells (particularly macrophages and neutrophils subsets) shape the protective vs deleterious immune response.
• Challenge to control for host genetics, pathogen genetics, dose, route, concurrent infection(s) and other environmental risks.
• Exploring the mechanisms involved in pathogen killing, granuloma formation, and control of bacterial dissemination.
• Understanding the mechanisms by which M. bovis evades or suppresses the host CMI response.

What approaches could/should be taken to address the research question?

Characterizing the cytokine profiles produced by T cells and other immune cells during infection.
Identifying the key cytokines involved in the immune response, their timing and levels of production, and their correlation with disease outcome and progression.
Investigating the effector mechanisms employed by cytotoxic T lymphocytes (CTLs) and other immune cells in combating bTB infection.
Studying the development and maintenance of memory T cell responses following bTB.
Exploring the longevity, functional properties, and protective potential of memory T cells in providing long-term immunity and protection against reinfection.
Comparative studies across different host species, such as cattle and other animal models, can provide insights into conserved and species-specific aspects of the CMI response to bTB.
Control for host genetic background; be aware of spectrum of responses.
Investigating the interactions between all the above T cell subsets and innate immune cells (particularly macrophages and neutrophils subsets) during the different stages of the immune response, in susceptible versus resistant animals
Looking into the antigenic variation, immune evasion strategies, and mechanisms of immune tolerance employed by the bacterium will aid in designing effective interventions.

What else needs to be done before we can solve this need?

Improved understanding of host-pathogen interactions.
Availability of suitable immunological reagents at a price that would make test suitable for widespread use.
Set up cohorts of animals for longitudinal follow-up of animals in the field

Existing knowledge including successes and failures