A newborn mouse model for the study of intestinal pathogenesis of shigellosis

Abstract

SummaryShigella infection is characterized by the induction of acute inflammation, which is responsible for the massive tissue destruction of the intestinal mucosa. A murine model would be a valuable tool for gaining a better understanding of the physiopathology of shigellosis and the host immune response to Shigella infection, but adult mice do not develop disease upon oral inoculation. We therefore attempted to develop a model of infection in newborn mice. Four-day-old mice inoculated with 50 m m m m l of 5 ¥ ¥ ¥ ¥ 10 9 invasive wild-type Shigella flexneri 5a were susceptible to bacterial infection, but mice inoculated with the non-invasive strain BS176 were not. Histologically, 4-day-old mice infected with the invasive strain presented intestinal lesions and inflammation similar to those described in patients with shigellosis. Moreover, cytokine and chemokine responses consistent with inflammation were observed. Lower bacterial inocula induced less severe intestinal damage. In contrast, 5-day-old mice inoculated with either the invasive or the non-invasive strain were not infected. We have thus established a mouse model that is suitable for the study of the pathogenesis of intestinal Shigella infection.

New Animal Model of Shigellosis in the Guinea Pig: Its Usefulness for Protective Efficacy Studies

“…However, the major drawback of this model is the lack of clinical relevance to the infection site. Recently, Sansonetti and colleagues (39) have been able to develop a model of intragastric infection in newborn mice using massive amounts of Shigella (10 9 CFU). This murine infection model led to inflammatory destruction of the mucosa and significant infiltration of PMNs into the gut, but it cannot be used to evaluate protective immunity because the model must be used within a narrow window of time, i.e., 4 -5 days following birth.…”

Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice

“…After 8 h of starvation (35,36), animals were inoculated i.p. with 50 ml nonimmune or immune sera (BLS-Stx2B+FA, 45 d post last immunization, diluted 1:100 in PBS) and intragastrically inoculated via a stainless steel cannula (0.38 mm 3 22G) (model 7.7.1; Harvard Apparatus, Holliston, MA) with 0.1 ml bacterial suspension (4 3 10 11 CFU/kg).…”

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

“…This exquisite susceptibility to infection during neonatal life includes both peripheral and mucosal routes of infection. In particular, neonatal animals succumb rapidly to pulmonary infection with Streptococcus pneumoniae (24) and gastrointestinal infection with enteropathogens including Vibrio cholerae (10), Aeromonas hydrophila (76), Shigella flexneri (23), enterotoxigenic E. coli (19), and Salmonella species (15,61). Thus, mucosal immune responses to most pathogens studied to date are severely compromised in early life.…”