Immune response of bighorn sheep to Mannheimia haemolytica
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Bighorn sheep (BHS; Ovis canadensis) are more susceptible to Mannheimia haemolytica-caused pneumonia, than domestic sheep (DS; Ovis aries). The objective of this study was to elucidate the basis for enhanced susceptibility of BHS, and explore potential strategies to prevent pneumonia in BHS. I hypothesized that enhanced lung pathology in BHS is due to inadequate clearance of M. haemolytica from the lungs. To test this hypothesis, M. haemolytica was inoculated intra-tracheally into groups of BHS and DS that were necropsied at 4, 12, and 18 hours post-inoculation (hpi). DS completely cleared the bacteria from the lungs by 18 hpi, whereas BHS had large number of bacteria still remaining in the lungs. Furthermore, bronchoalveolar lavage fluid from BHS had significantly lower titers of neutralizing antibodies to leukotoxin, the critical virulence factor of M. haemolytica. These findings suggested that enhanced lung pathology in BHS is likely due to inadequate clearance from the lungs, which, at least partly, is due to low titer of leukotoxin-neutralizing antibodies. In another study, serine protease inhibitor B1 of BHS and DS was cloned and expressed to facilitate future studies on the role of protease-anti-protease imbalance in enhanced susceptibility of BHS to M. haemolytica-caused pneumonia. M. haemolytica are more frequently isolated from nasopharynx of DS than that of BHS. Furthermore, most DS isolates are leukotoxin-positive whereas most BHS isolates are leukotoxin-negative, which is likely responsible for the negligibly low titers of leukotoxin-neutralizing antibodies in BHS. A `proof-of-concept' study was designed to determine whether repeated immunization will protect BHS against M. haemolytica challenge. Four BHS were repeatedly inoculated with a vaccine prepared with M. haemolytica A1, A2, and Bibersteinia trehalosi T10 culture supernatant. Upon subsequent challenge with M. haemolytica, all four vaccinated animals survived while all four un-vaccinated animals died within two days, suggesting that BHS are capable of mounting protective immune response against M. haemolytica. This notion was confirmed by another study that showed that MHC class II diversity in BHS is comparable to that of DS. Therefore, induction of immunity to M. haemolytica, particularly to its leukotoxin, is likely to protect BHS against pneumonia caused by this organism.