Yersinia enterocolitica infection in humans causes a broad spectrum of diseases ranging from acute bowel disease to extraintestinal manifestations such as
reactive arthritis,
erythema nodosum and
uveitis. During the last decade a fascinating part of the molecular biology of the pathogenicity of human pathogenic Yersinia species has been unraveled.
Pathogenicity factors such as
protein tyrosine phosphatase,
protein kinase,
thrombin- and
collagen-binding factors have been identified and characterized on the molecular level. In contrast to many animal models for human enteropathogenic microorganisms, experimental Y. enterocolitica
infection in rodents resembles
yersiniosis in humans and thus offers extraordinary opportunities to study the sequential steps of the infectious process. Rabbits are suitable animals in which to study Yersinia-induced
enteritis (
enterotoxin-mediated) and the humoral immune response after oral
infection. The role of Peyer's patches (PP) in the entry of enteropathogenic Yersinia species has been elucidated in mice and rabbits. M cells are probably the primary target cells of invading Yersiniae. Surprisingly, after penetration of the mucosal epithelial cell layer Yersinia bacilli were visualized to be exclusively extracellular in PP tissue. Obviously neutrophils within PP were unable to phagocytize the invading microorganisms. Presently, it is not clear how the microorganisms disseminate from PP into lymph nodes, spleen, liver and lung of mice where they form
abscesses and
granuloma-like lesions. Immunohistologically the involvement of macrophages and T cells could be demonstrated in Yersinia-induced lesions of mice. Direct evidence for the role of T cells and
cytokine-activated macrophages in the host defense reaction against a primary
Yersinia infection in mice could be obtained from experiments including adoptive transfer of Yersinia-specific T cells and in vivo neutralization of
TNF-alpha and IFN-gamma. The experimental rat model turned out to be a suitable model for studying Yersinia-induced aseptic
arthritis. Lewis- and SHR rats proved to be
arthritis-susceptible. Arthritogenicity of Yersinia for rats appeared to be restricted to Y. enterocolitica of serotype 08 and correlated with the virulence potential of this serotype. Surprisingly, expression of YadA, the
collagen-binding factor, was not necessary for
arthritis induction. A close association between both susceptibility to
arthritis induction and
Yersinia infection could be demonstrated in various rat strains. Depletion of
alpha/beta T-cell receptor (
alpha beta-TCR)-positive T cells by treatment with
alpha beta-TCR-specific antibody revealed that T cells were required for clearance of the pathogen.(ABSTRACT TRUNCATED AT 400 WORDS)