Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Abe, Jun; Onimaru, Michiko; Matsumoto, S; Noma, Seiji; Baba, Kiyoshi; Ito, Yasuhiko; Kohsaka, Takao; Takeda, Tae

doi:10.1172/jci119349

Cited by 75 publications

(45 citation statements)

References 60 publications

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“…Pathogenic Yersinia can be divided into low pathogenic strains, which induce a mild intestinal infection in humans, and highly pathogenic strains, which cause severe systemic infection in humans [4,10]. Whether pathogenic Yersinia causes limited gastroenteritis or systemic infection in humans correlate with the presence of a high-pathogenicity island (HPI), encoding an iron uptake system represented by its siderophore yersiniabactin [4] or Y. pseudotuberculosisderived mitogen (YPM), which is a superantigenic toxin [1]. It is known that the presence of YPM is limited to the Far East (Japan, Korea and Far-Eastern Russia) [10], and in Japan, Y. pseudotuberculosis harboring YPM were isolated from almost all the fatal cases of breeding monkeys [14].…”

Section: Discussionmentioning

confidence: 99%

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Iwata

Une

Lee

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. To investigate the prevalence of antibodies to pathogenic Yersinia in breeding squirrel monkeys, the serum samples of 252 squirrel monkeys from 9 zoological gardens in Japan were tested by ELISA using plasmid-encoded Yersinia outer membrane protein (Yops) as the antigen. The cutoff value was calculated by using the serum samples of the squirrel monkeys from Suriname, where no prevalence of pathogenic Yersinia have been reported. According to the cutoff value, 164 of 252 (65.1%) squirrel monkeys were considered positive against pathogenic Yersinia. These positive monkeys belonged to 8 of the 9 zoological gardens, and the percentage of the seropositive monkeys ranged from 22.2 to 89.4%. Furthermore, in one zoological garden, the positive rate of the squirrel monkeys which were over 1 year old (95.7%) was significantly higher than those which were under 1 year old (23.3%). These results suggested that pathogenic Yersinia is highly prevalent among breeding monkeys in Japan.

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Section: Discussionmentioning

confidence: 99%

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Iwata

Une

Lee

et al. 2010

The Journal of Veterinary Medical Science

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“…Interestingly, YPM-producing Y. pseudotuberculosis strains are more frequently found in the Far East, where the clinical symptoms of Y. pseudotuberculosis infections are more di-verse and more severe than those observed in Europe (fever and mild gastrointestinal disorders) (21). It has been reported that 61% of patients with acute Y. pseudotuberculosis infections have anti-YPM antibodies and that the V␤3-bearing T cell count rises markedly during infection-emphasizing the production of YPM in vivo and its impact on the human immune system (22). In mice, injection of purified YPM toxin can induce lethal shock in both BALB/c and C57BL/6 strains (11,23).…”

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Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4⁺T Cells

et al. 2015

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V␤7؉ T cell expansion and marked interleukin-4 (IL-4) production in mice inoculated with SAg-producing Y. pseudotuberculosis. These phenomena were correlated with the activation of ypm gene transcription in liver and spleen. A transcriptomic analysis revealed that the presence of YPM also increased expression of granzyme and perforin genes in the host's liver and spleen. This expression was attributed to a CD4 ؉ T cell subset, rather than to natural killer T (NKT) cells that display a TcR with a V␤ region that is potentially recognized by YPM. Increased production of cytotoxic molecules was correlated with hepatotoxicity, as demonstrated by an increase in plasma alanine aminotransferase activity. Our results demonstrate that YPM activates a potentially hepatotoxic CD4؉ T cell population.

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“…Furthermore, V␤3-bearing T cells were increased in patients during the acute phase of the disease (2). Additionally, Miyoshi-Akiyama et al (32) found that purified YPMa was able to induce lethal shock in a murine experimental model, demonstrating the toxicity of the Y. pseudotuberculosis superantigenic toxin in vivo.…”

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confidence: 99%

“…A recent study showed that 61% of patients acutely infected with Y. pseudotuberculosis, especially those with systemic complications, had elevated anti-YPM immunoglobulin G level in blood, thereby demonstrating the production of YPMa in vivo (2). Furthermore, V␤3-bearing T cells were increased in patients during the acute phase of the disease (2).…”

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confidence: 99%

Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

et al. 2000

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The gram-negative bacterium Yersinia pseudotuberculosis is widely spread in nature and is responsible for sporadic infection in many animal species (10). Humans are commonly infected after ingestion of food or water contaminated with excreta of infected animals. Y. pseudotuberculosis causes acute ileitis and mesenteric lymphadenitis, sometimes complicated by septicemia (10, 26), but is also responsible for the occurrence of postinfection complications such as reactive arthritis and erythema nodosum (10,35,45,46). This microorganism has been suggested as one of the causative agents of Kawasaki syndrome, an acute, self-limited vasculitis affecting predominantly infants and young children (4,25,39). A few years ago, Y. pseudotuberculosis strains producing a mitogen activity were isolated from a mass outbreak in Japan (48) and from a patient with Kawasaki-like symptoms (1, 51). The substance, purified from bacterial lysates and exhibiting a mitogenic activity on human peripheral blood mononuclear cells (PBMC), was first designated YPM, for Y. pseudotuberculosis-derived mitogen (30), and then YPMa after the discovery of a variant (36). YPMa was characterized as a 14.5-kDa superantigenic toxin activating human T lymphocytes bearing T-cell receptors exhibiting the V␤3, V␤9, V␤13.1, and V␤13.2 variable regions (1, 48). The geographic distribution of the 456-bp superantigenencoding gene ypmA is rather heterogeneous, being present in most Y. pseudotuberculosis strains from the Far East but only in about 20% of European clinical isolates (13,52).A recent study showed that 61% of patients acutely infected with Y. pseudotuberculosis, especially those with systemic complications, had elevated anti-YPM immunoglobulin G level in blood, thereby demonstrating the production of YPMa in vivo (2). Furthermore, V␤3-bearing T cells were increased in patients during the acute phase of the disease (2). Additionally, Miyoshi-Akiyama et al. (32) found that purified YPMa was able to induce lethal shock in a murine experimental model, demonstrating the toxicity of the Y. pseudotuberculosis superantigenic toxin in vivo. The toxin was also found to alter in vitro epithelial function by reducing active ion transport and increasing epithelial permeability (16). Altogether, these data suggest a role of YPMa in the pathogenesis of Y. pseudotuberculosis infections, but experimental evidence necessary to confirm this hypothesis is lacking. In this study, we constructed a superantigen-deficient mutant of Y. pseudotuberculosis and tested its virulence in a mouse experimental model of infection. Rodents have been extensively used as the animal model to study Yersinia infections since they develop a disease resembling yersiniosis in humans (22). We found that inactivation of ypmA reduced the virulence of Y. pseudotuberculosis after intravenous (i.v.) challenge but not after intragastric (i.g.) inoculation, demonstrating an exacerbated toxicity of YPMa-producing Y. pseudotuberculosis in systemic infection. MATERIALS AND METHODSBacterial strains, growth ...

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Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Cited by 75 publications

References 60 publications

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4⁺T Cells

Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

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Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Cited by 75 publications

References 60 publications

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Seroepidemiological Survey of Pathogenic Yersinia in Breeding Squirrel Monkeys in Japan

Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4+T Cells

Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

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Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4⁺T Cells