Introduction: Urinary Tract Infections (UTIs) are a huge public health problem affecting an estimated 300 million people each year worldwide [1]. UTIs are predominantly caused by uropathogenic Escherichia coli (UPEC). A protective role for the regulatory cytokine IL-10 in the control of acute UTI has previously been demonstrated [2], however, UPEC factor(s) associated with IL-10 induction have yet to be identified. We hypothesized that UPEC flagellin (FliC), the major flagellar filament protein contributes to the induction of IL-10 during acute UTI.
Methods: UPEC reference strain CFT073 and their fliC mutant were used [3]. Extraction and purification of FliC to homogeneity was performed using a protocol based on sequential steps of mechanical shearing, ultracentrifugation, and chromatography. Human U937 monocytes and J774 mouse macrophages were used to define the biological activity of native FliC. RNA sequencing was applied to map the transcriptomic response of the bladder in response to FliC in female C57Bl/6 and TLR5-/- mice.
Results: UPEC CFT073 derivatives and purified FliC induces significant amount of IL-10 within 5h of infection in both in-vitro and in-vivo studies. Transcriptomic data demonstrate significant IL-10 upregulation in the bladder in response to FliC among other innate responses consistent with prior literature. Additionally, it revealed multiple host factors not previously reported to be associated with host responses to FliC.
Conclusion: We propose that flagellin of UPEC contributes to early immune regulatory cascades via IL-10 induction. These findings may be useful to identify potential targets for manipulating the infectious process and disease pathogenesis.