Histopathology of Experimental Plague in Cats

Watson, Rowena P.; Blanchard, Terrell W.; Mense, Mark G.; Gasper, Peter W.

doi:10.1354/vp.38-2-165

Cited by 24 publications

(10 citation statements)

References 26 publications

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“…In studies of the pathogenesis of Y. pestis infection workers have used a number of different animal models (4,5,13,14,19,31,37). Currently, there is no consensus concerning which model system is best.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies workers used a number of different hosts to experimentally study Y. pestis infection, including nonhuman primates, cats, and rodents (mice and rats), each of which has advantages and disadvantages (4,5,13,14,19,31,37). The utility of rodent models, particularly mice, make them attractive models, as rodents are natural hosts of Y. pestis and have been used extensively in studies of both pathogenesis and the efficacy of vaccines against Y. pestis infection using both bubonic (22,26) and pneumonic (36,39) models.…”

mentioning

confidence: 99%

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Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

2007

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Yersinia pestis is the causative agent of plague, a disease that can manifest as either bubonic or pneumonic plague. An interesting feature of plague is that it is a rapidly progressive disease, suggesting that Y. pestis either evades and/or suppresses the innate immune response to infection. Therefore, the early host response during the course of primary pneumonic plague was investigated in two mouse strains, the outbred strain CD1 and the inbred strain C57BL/6. A comparative analysis of the course of disease in these two strains of mice indicated that they are susceptible to intranasal Y. pestis CO92 infection and have similar 50% lethal doses and kinetics of infection with respect to colonization of the lung, liver, and spleen. Significantly, in both strains of mice, robust neutrophil recruitment to the lungs was not observed until 48 h after infection, suggesting that there was a delay in inflammatory cell recruitment to the site of infection. In addition, proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, gamma interferon, IL-12p70, monocyte chemoattractant protein 1) and chemokines (KC, MIP-2) in the bronchoalveolar lavage fluids were not readily detected until 48 h after infection, which coincided with the increase in polymorphonuclear leukocyte (PMN) recruitment to the lungs. In comparison, CD1 mice with gram-negative pneumonia caused by Klebsiella pneumoniae exhibited strong inflammatory responses early in infection, with PMNs comprising the majority of the cells in the bronchoalveolar lavage fluid 24 h postinfection, indicating that PMN recruitment to the lungs could occur earlier in this infection than in Y. pestis infection. Together, our results indicate that there is a delay in the recruitment of neutrophils to the lungs in the mouse model of primary plague pneumonia that correlates with delayed expression of proinflammatory cytokines and chemokines in both outbred and inbred mice.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

2007

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“…On the other hand, to assess the animal models of bubonic plague, pathological characteristics during bubonic infection have been investigated in mice [6], cats [7] and guinea pigs [3]. Pneumonic plague is the form most likely to be observed in biological warfare or bioterrorism events and interest in animal models has been raised to support plague therapeutic and vaccine studies.…”

Section: Introductionmentioning

confidence: 99%

Histopathological Observation of Immunized Rhesus Macaques with Plague Vaccines after Subcutaneous Infection of Yersinia pestis

et al. 2011

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In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

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“…However, in marmots, a challenge dose of 1.0×10 5 CFU causes 100% death in experimental animals [23]. The susceptibility of great gerbils to Y. pestis infection is much lower than that of Citellus undulatus , Citellus dauricus , Rattus flavipectus , prairie dogs, and cats [12], [24], [25]. Although different Y. pestis strains were used for these animal challenge experiments, these results could indicate the different levels of susceptibility of various reservoirs to this pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical symptoms of infected great gerbils were different from those of infected mice, guinea pigs, and cats [24], [25]. The anal temperature increased quickly within the first three days p.i., before it gradually decreased to normal on day 7 p.i.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Yersinia pestis and Its Antibody Response in Great Gerbils (Rhombomys opimus) by Subcutaneous Infection

et al. 2012

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Background Rhombomys opimus (great gerbil) is a reservoir of Yersinia pestis in the natural plague foci of Central Asia. Great gerbils are highly resistant to Y. pestis infection. The coevolution of great gerbils and Y. pestis is believed to play an important role in the plague epidemics in Central Asia plague foci. However, the dynamics of Y. pestis infection and the corresponding antibody response in great gerbils have not been evaluated. In this report, animal experiments were employed to investigate the bacterial load in both the liver and spleen of infected great gerbils. The dynamics of the antibody response to the F1 capsule antigen of Y. pestis was also determined.MethodologyCaptured great gerbils that tested negative for both anti-F1 antibodies and bacterial isolation were infected subcutaneously with different doses (105 to 1011 CFU) of a Y. pestis strain isolated from a live great gerbil during routine plague surveillance in the Junggar Basin, Xinjiang, China. The clinical manifestations, changes in body weight, anal temperature, and gross anatomy of the infected animals were observed. The blood cell count, bacterial load, and anti-F1 antibody titers were determined at different time points after infection using a blood analyzer, plate counts, and an indirect hemagglutination assay, respectively.Conclusions/SignificanceThe dynamics of bacterial load and the anti-F1 antibody concentration in great gerbils are highly variable among individuals. The Y. pestis infection in great gerbils could persist as long as 15 days. They act as an appropriate reservoir for plague in the Junggar Basin, which is part of the natural plague foci in Central Asia. The dynamics of the Y. pestis susceptibility of great gerbil will improve the understanding of its variable resistance, which would facilitate the development of more effective countermeasures for controlling plague epidemics in this focus.

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Histopathology of Experimental Plague in Cats

Cited by 24 publications

References 26 publications

Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

Histopathological Observation of Immunized Rhesus Macaques with Plague Vaccines after Subcutaneous Infection of Yersinia pestis

Dynamics of Yersinia pestis and Its Antibody Response in Great Gerbils (Rhombomys opimus) by Subcutaneous Infection

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