Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner
Fig 6
Depletion of CD4+ and CD8+ T cell subsets increases chronic and recurrent CFT073 cystitis.
Mice infected with 108 CFU UTI89 or CFT073 were given weekly doses of anti-CD4 and anti-CD8 antibodies, or isotype control, and followed for four weeks. (A) The incidence of chronic cystitis was determined at 28 dpi; # indicates the number of mice per group. (B) Urine bacterial burdens at 28 dpi. (C) CFT073-infected mice from (A) were binned according to the length of their infection. ** P < 0.01, Fisher’s exact test for resolving 8–28 dpi. (D) CFT073 urine titers over the course of infection from isotype-treated (left panel) and anti-CD4/8-treated (right panel) mice. Dashed lines indicate our previously established cutoff for high-titer persistent bacteriuria, 104 CFU/ml urine. (E) Shown are the percentages of mice with persistent high-titer CFT073 bacteriuria (>104 CFU/ml urine) over time. (F-J) At 28 dpi, antibiotic therapy was initiated. Those mice that developed chronic cystitis during the initial infection were then challenged four weeks after antibiotics with 107 CFU of the same strain as their initial infection. Depletion antibodies were not administered during the challenge infection. (F) The incidence of recurrent chronic cystitis was determined at four weeks post challenge; # indicates the number of mice per group. (G) CFT073 urine titers over the course of the challenge infection in CFT073HC mice, from mice initially isotype-treated (left panel) and initially anti-CD4/8-treated (right panel). Some samples were unavailable at three days post challenge. (H) Shown are the percentages of CFT073HC mice with persistent high-titer recurrent CFT073 bacteriuria (>104 CFU/ml urine) during the challenge infection. (I and J) Shown are bladder and kidney bacterial burdens (I) and bladder edema (J) at time of sacrifice. Data are combined from two to four independent experiments; data points represent actual values for each individual mouse, zeros are plotted at the limit of detection, and bars indicate median values. *, P < 0.05, Mann-Whitney U test. rUTI, recurrent urinary tract infection.