Download Pathogenesis of pneumonic pasteurellosis: Host

PATHOGENESIS OF PNEUMONIC PASTEURELLOSIS: HOST-BACTERIAL
INTERACTIONS AND PREVENTION OF DISEASE
Anthony W. Confer, DVM, PhD
Oklahoma State University
College of Veterinary Medicine
Stillwater, OK 74078
Pasteurella haemolytica (recently renamed Mannheimia haemolytica) is the
bacterium most frequently isolated from Shipping Fever, a severe fibrinous
pleuropneumonia of cattle. Due to the role of P. haemolytica, Shipping Fever is
usually referred to as bovine pneumonic pasteurellosis. P. haemolytica Serotype
1 is isolated most often from bovine pneumonic pasteurellosis. The pathogenesis
of P. haemolytica relies on stress factors – such as shipping - and/or viral
infections that set in motion several bacterial-host interactions that can lead to
pneumonic pasteurellosis. These include nasopharyngeal colonization,
inhalation, pulmonary alveolar colonization, host response to colonization, and
bacterial evasion of host defense.
This review will discuss the following:
 Current knowledge and understanding of bacterial-host interactions in the
nasopharynx and pulmonary alveoli that lead to pneumonic pasteurellosis,
 Pathogenic roles that known and potential virulence factors of P.
haemolytica play or potentially play in those interactions,
 Host inflammatory and immune responses to various virulence factors,
 Potential vaccine strategies using our current knowledge.
Various P. haemolytica virulence factors influence the outcome of bacterialhost interactions. The pathogenic roles of several of those factors are
documented. Those factors are endotoxin (lipopolysaccharide [LPS]), leukotoxin
(LKT), and capsular polysaccharide (CPS). Other potential virulence factors
whose roles are less well documented or not defined include: fimbriae, outer
membrane proteins (OMPs), iron-regulated proteins, serotype-specific
agglutinating antigen, neuraminidase, and neutral glycoprotease, superoxide
dismutase, 54-kDa heat-shock protein, and IgG1-specific protease.
Most of our understanding of the potential roles of these virulence factors
comes from in vitro experiments. Through those experiments, we have learned
how LKT, CPS, endotoxin and others interact with isolated cell populations such
as leukocytes and endothelium. Virulence factors may cause target cell death by
apoptosis or cell lysis. In addition, virulence factors often cause macrophages
and other cells to produce cytokines, to release nitric oxide, oxygen-free radicals,
or histamine, or to modify coagulation and cell adhesion. In recent years, we
have learned more about the localized and systemic reactions of cattle when P.
haemolytica colonizes the lung. These responses include cytokine, immune,
prostanoid, leukotriene, and acute-phase protein responses. However, we have
been unable to critically define the roles of many individual virulence factors in
vivo. This is due to the complexity of the bacterial-host interactions in pneumonic
pasteurellosis, the lack of a suitable laboratory animal model that mimics bovine
pneumonic pasteurellosis, and the lack of protection of cattle after vaccination
with purified factors (CPS or LKT). Limited in vivo studies of the pathogenesis of
pneumonic pasteurellosis have been conducted using mutant strains of P.
haemolytica that are deficient in individual virulence factors. In vivo testing of
those bacterium both as vaccines and challenge strains should allow us to better
determine the pathogenic role of individual virulence factors within the complexity
of the living animal.
Current vaccine strategies are aimed at stimulating a systemic antibody
response that neutralizes LKT and binds bacterial surface antigens thereby
functioning as opsonins or in complement-mediated killing. Controversy exists
as to what are the important surface antigens that must be included in a P.
haemolytica vaccine. CPS, LPS and OMPs have been considered candidates
for that role. We and others, however, have failed to demonstrate significant or
consistent association between antibodies to CPS or LPS and protection against
experimental pneumonic pasteurellosis. OMPs seem to be good candidates for
stimulating protective immunity to the surface antigens of the bacterium.
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