New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies.

J Immunol 2007 Feb;178(4):2476-82

Mucosal Immunology Section, International Vaccine Institute, Seoul, Korea.

It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form of bacillary dysentery caused by Shigella spp. infection, because of the lack of suitable animal models. To develop a proper animal model representing human bacillary dysentery, guinea pigs were challenged with virulent Shigella flexneri serotype 2a (strains 2457T or YSH6000) or S. flexneri 5a (strain M90T) by the intrarectal (i.r.) route. Interestingly, all guinea pigs administered these Shigella strains developed severe and acute rectocolitis. They lost approximately 20% of their body weight and developed tenesmus by 24 h after Shigella infection. Shigella invasion and colonization of the distal colon were seen at 24 h but disappeared by 48 h following i.r. infection. Histopathological approaches demonstrated significant damage and destruction of mucosal and submucosal layers, thickened intestinal wall, edema, erosion, infiltration of neutrophils, and depletion of goblet cells in the distal colon. Furthermore, robust expression of IL-8, IL-1beta, and inducible NO synthase mRNA was detected in the colon from 6 to 24 h following Shigella infection. Most importantly, in our new shigellosis model, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain possessing high levels of mucosal IgA Abs showed milder symptoms of bacillary dysentery than did animals receiving PBS alone after Shigella infection. In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates.

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.178.4.2476DOI Listing
February 2007
17 Reads

Publication Analysis

Top Keywords

bacillary dysentery
12
protective efficacy
12
shigella infection
12
animal model
12
guinea pigs
12
shigella
9
distal colon
8
vaccine candidates
8
guinea pig
8
guinea
5
infection
5
route interestingly
4
animal
4
shigella invasion
4
iga abs
4
mrna detected
4
infection shigella
4
invasion colonization
4
animals receiving
4
infection histopathological
4

References

(Supplied by CrossRef)

Infect. Dis. Clin. North. Am. 1988

Infect. Immun. 1996

Infect. Immun. 1989

J. Bacteriol. 1993

Am. J. Pathol. 1968

Gastroenterology 1986

Similar Publications