Activation of macrophages in an experimental rat model of arthritis induced by Erysipelothrix rhusiopathiae infection

Abstract

Infection of Lewis rats with Erysipelothrix rhusiopathiae represents an experimental model system of acute and chronic arthritis. We studied here the acute inflammatory phase with respect to stimulation of macrophages and lymphocytes. Intragluteal injection of viable E. rhusiopathiae (102 to 104 bacteria) rapidly induced generalized inflammation, loss of body weight, hind leg arthritis, and systemic macrophage activation within 2 to 3 days. The same symptoms could also be evoked by injection of dead E. rhusiopathiae. Ex vivo, peritoneal macrophages released large amounts of tumor necrosis factor alpha on day 2 and interleukin-1 on day 3, whereas production of prostaglandin E2 was delayed to days 5 to 7 and appeared to counteract tumor necrosis factor alpha synthesis. The inflammatory response and development of arthritis were strongly dependent on T lymphocytes, as evidenced by the following findings: (i) lymphocytes released lymphokines that activated macrophages to enhanced mediator release; (ii) treatment of rats with cyclosporin A reduced infection-induced macrophage activation; (iii) mitogen-stimulated thymocyte proliferation was enhanced, indicating an infection-induced maturation-differentiation process in the thymus; and (iv) in T-cell-deficient nude rats, a higher dose of bacteria was required for infection, the inflammatory response was less severe, and only mild, but not chronic, arthritis developed. Thus, an E. rhusiopathiae-induced inflammation in rats provides a useful tool to characterize activated macrophages and T lymphocytes during the development of acute arthritis and its transition into the chronic form.

Pathology, microbiology, and genetic diversity associated with Erysipelothrix rhusiopathiae and novel Erysipelothrix spp. infections in southern sea otters (Enhydra lutris nereis)

“…Laboratory models have also been used to investigate the pathogenesis of Erysipelothrix spp. infections and compare virulence of species or strains in different hosts, including swine ( To H et al, 2010 ), mice ( Zhu et al, 2018 ), rats ( Renz et al, 1989 ), chickens ( Wattrang et al, 2020 ), and fish ( Pomaranski et al, 2018 ). In vivo models that facilitate study of disease in a controlled environment, such as experimental infection of tiger barbs ( Puntigrus tetrazona ) can facilitate comparison of virulence between Erysipelothrix spp.…”

Characterization of a protective protein antigen ofErysipelothrix rhusiopathiae

“…However, chronic swine erysipelas characterized by polyarthritis is still frequently diagnosed in vaccinated herds and this raises the question as to whether vaccination leads to excessive local immune responsiveness of the synovial tissue to infection derived from field exposure [8]. The resemblance of porcine erysipelas polyarthritis to human rheumatoid arthritis has also inspired the suggestion that the arthritic pig might serve as a model for the study of the disease in humans [9][10][11][12]. E.…”

The significance of Spa-type represented in swine Erysipelothrix rhusiopathiae bacterins for cross-protection against erysipelas

“…Chronic erysipelas usually follows an acute or subacute infection where selfsustaining destructive pathological changes can occur in the heart valves and joints producing endocarditis and arthritis, respectively [10,28,29]. Arthritis caused by chronic erysipelas is considered an economic problem in the swine industry.…”

“…The development of erysipelas-induced arthritis is considered to be dependent on cell-mediated immune responses [28,29,31,32], and because of the physiological similarities, chronically affected animals have been regarded as valuable models for studying human rheumatoid arthritis [28,29]. A study by Renz et al [29] utilized rats to demonstrate the sequence of events that characterize the acute phase of E. rhusiopathiaeinduced arthritis. It was shown that the inflammatory response leading to the development of arthritis was strongly dependent on the organism's interaction with macrophages and T lymphocytes to enhance inflammatory mediator release.…”