Mycobacterium avium subsp. paratuberculosis (MAP) infection of cattle has a damaging economic impact and is a cause for concern regarding potential zoonotic transmission. There are significant difficulties regarding preventing, detecting, and eradicating MAP infection in cattle herds, many of which stem from the ability of MAP to evade the host immune response (and thus diagnosis). This evasion is associated with the ability of MAP to persist within macrophages for prolonged periods of time. The precise mechanisms of this host-pathogen interaction are not fully understood; we hypothesise that the earliest interactions between MAP and host macrophages, including the mechanism of uptake, may play a pivotal role in determining the outcome of infection. In order to investigate this, we infected bovine monocyte derived macrophages (MDM) with two strains of MAP (the well-established K10 strain and strain C49, a recent clinical isolate from cattle) in order to model the infection in vitro. Following infection of MDM with the C49 strain, numbers remained fairly constant over a 24 hour time-course, whereas the K10 strain was completely eradicated by 24 hours post infection; this difference in survival is indicative of a loss of virulence in the K10 strain through lab adaptation. Due to the difference observed between the two strains in their ability to survive intracellularly, the early immune response of MDMs to each strain was analysed, shedding light on mechanisms which could be important for early clearance. By assessing cell surface molecule expression, gene expression, cytokine secretion, nitrite and reactive oxygen species production and phagosome acidification, a detailed picture of the early macrophage response was formed for both strains. We also demonstrated that the presence of serum antibody responses to MAP can impact uptake and survival of MAP within macrophages and impact their downstream effector functions. This suggests that the mechanism of uptake, for example via Fc or complement receptors, could play a role in determining downstream responses to MAP infection.
|Conference||14th International Colloquium on Paratuberculosis|
|Period||20/06/16 → …|