Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and cattle. The bacterium produces several virulence factors,whose principal ones are lipopolysaccharide and leukotoxin. The latter is cytotoxic only for ruminant leukocytes, a phenomenon that is correlated with its ability to bind and interact with the ruminant beta2-integrin Lymphocyte Function-associated Antigen 1. This paper globally reviews all the information available on host-pathogen interactions underlying respiratory mannheimiosis (formerly pasteurellosis), from the stable and the Petri dish to the biochemical cascade of events triggered by the leukotoxin inside ruminant leukocytes. One conclusion can be made: the most widespread cattle respiratory disease with the most important impact on beef production worldwide, is probably due to a tiny ruminant-specific focal variation in the CD18- and/or CD11a-expressing genes.