# Temporal dynamics of the early immune response following Mycobacterium bovis infection of cattle

## TL;DR

This study examines how the immune system of cattle responds early after infection with Mycobacterium bovis, showing that immune responses can be detected within weeks.

## Contribution

The study provides new insights into the timing and patterns of immune responses using modern diagnostic assays in cattle infected with M. bovis.

## Key findings

- Cell-mediated immune responses were detectable in all infected cattle by three weeks post-infection.
- Six out of eight infected animals showed early antibody responses by four weeks post-infection using the Enferplex TB assay.
- Fecal shedding of M. bovis was infrequent and not linked to immune response patterns.

## Abstract

Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.