Ingénierie génétique d'une β2-intégrine LFA-1 bovine résistante à la leucotoxine de Mannheimia haemolytica

Domesticated bovines are known since decades to be prone to bacterial pneumonias. Among the causative agents, a consensus emerged stating that Mannheimia haemolytica is the most frequent bacterium isolated from bovine lungs throughout the world. Moreover, it appeared that its virulence specifically targets ruminant lungs in vivo and ruminant leucocytes in vitro. When the thesis was started, the two main actors underlying this species-specific virulence were known: the leukotoxin (LKT) on the pathogen side and the beta2-integrin LFA-1 on the host side. The objective of the thesis was to contribute to the understanding of the LKT/LFA 1 interaction at the molecular level. Using a between-species perspective, we showed that (i) the CD11a subunit of the LFA-1 heterodimer was not involved in the LKT-specificity for ruminant LFA-1, (ii) the EGF-3 module within the CD18 controls the susceptibility of any given CD18 to LKT and (iii) a non cleavable signal peptide conjugated to a LKT susceptible EGF-3-containing CD18 exacerbates LKT pronecrotic effects.