Figure 1.
Persistent Salmonella infection in mice.
(A) Flow chart of the experimental design. (B) Chronic Salmonella infection was measured by fecal matter analysis. In a BBL CHROMagar plate, intestinal Salmonella species appear mauve (rose to purple) in color, due to metabolic differences in the presence of selected chromogens. Other bacteria are either inhibited or produce blue-green or colorless colonies. Experimental groups: Control, normal wild-type mice; PhoPc, mice infected with Salmonella with normal AvrA expression; PhoPcAvrA−, mice infected with an AvrA− mutant derived from PhoPc; PhoPcAvrA−/AvrA+, mice infected with PhoPcAvrA− containing a complementary plasmid encoding AvrA. (C) Location of Salmonella in mouse intestine using immunofluorescence staining. Green staining in the mouse intestine shows the invasion of Salmonella in intestinal mucosa at 27 weeks postinfection.
Figure 2.
Physiologic changes after Salmonella infection.
(A) Changes in body weight after Salmonella infection. (B) The survival rate of mice after Salmonella Typhimurium infection for 27 weeks. N = 50 mice in each group. Mice were infected with indicated Salmonella Typhimurium strains for 27 weeks. Mice were weighted every week. If a mouse showed indications of aspirated fluid or significant body weight loss (10% or more), and did not die immediately, the mouse was humanely euthanized. The protocol was approved by the University of Rochester University Committee on Animal Resources (UCAR).
Table 1.
Body weight of mice infected with Salmonella for 27 weeks.
Figure 3.
Intestinal shortening induced by Salmonella in vivo.
(A) Length of ceca. (B) (C) Lengths of small intestine and colon. N = 50 mice in each group and 5–10 mice at each time point.
Figure 4.
Pathologic changes caused by the chronic Salmonella infection in streptomycin-pretreated mice.
(A) H & E staining of cecum in mice infected with S. Typhimurium at 1, 3, 6, 10 and 27 weeks postinfection compared to the wild-type mice (Control). C: Control; P: PhoPc; A-: PhoPcAvrA−; and A+: PhoPcAvrA−/AvrA+. (B) Histological score of cecal inflammation. Data are from three mice in each group at each time point. *, p<0.05.
Figure 5.
Liver and spleen affected by Salmonella infection in vivo.
(A) Weights of spleens in mice after Salmonella infection for 27 weeks. (B) Weights of livers in mice after Salmonella infection for 27 weeks. Data are from 5–10 mice in each group at each time point. **, p<0.01. ***, p<0.001. (C) Enlarged livers and spleens after Salmonella infection for 27 weeks.
Figure 6.
Numbers of Salmonella in different organs at 27 weeks postinfection in vivo.
(A) Feces. (B) Spleen. (C) Gallbladder. (D) Liver. N = 5 mice in each group.
Figure 7.
Salmonella translocation and infection in gallbladder and liver.
(A) Salmonella distribution in the gallbladder at 27 weeks after Salmonella infection. Salmonella: green staining (indicated with white arrows); nucleus: blue. (B) Liver abscess found in the PhoPc-infected mouse (indicated with an arrow). (C) Numbers of Salmonella in intestine at 18 hours post-infection.
Table 2.
Percentage of mice with liver abscess.
Figure 8.
Inflammatory cytokines in chronically Salmonella-infected mice.
The cytokines included CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p40/p70), IFN-γ, and TNF-α. They were tested in mouse serum using a mouse Cytokine 10-Plex Panel. * p<0.01. ** p<0.0005. Each single experiment was assayed in triplicate. Data are means ± SD of n = 4 mice in each group.
Table 3.
Salmonella strains used in this study.