Restriction of chronic Escherichia coli urinary tract infection depends upon T cell‐derived interleukin‐17, a deficiency of which predisposes to flagella‐driven bacterial persistence

Abstract

Urinary tract infections (UTI) frequently progress to chronicity in infected individuals but the mechanisms of pathogenesis underlying chronic UTI are not well understood. We examined the role of interleukin (IL)-17A in UTI because this cytokine promotes innate defense against uropathogenic Escherichia coli (UPEC). Analysis of UPEC persistence and pyelonephritis in mice deficient in IL-17A revealed that UPEC CFT073 caused infection at a rate higher than the multidrug resistant strain EC958. Il17a −/− mice exhibited pyelonephritis with kidney bacterial burdens higher than those of wild-type (WT) mice. Synthesis of IL-17A in the bladder reflected a combination of γδ-T and T H 17 cell responses. Analysis of circulating inflammatory mediators at 24h postinoculation identified predictors of progression to chronicity, including IL-6 and monocyte chemoattractant protein-1 (MCP-1). Histological

Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli

“…Rapid secretions of IL6 are conducive to innate immune response during infection, while the excessive release of IL6 is implicated in the course of inflammatory disorders ( Kang et al, 2019 ). In response to pathogens of UTIs, IL6 is primarily secreted by the host, followed by the release into the serum, thereby inducing a transcriptional inflammatory response through IL6 receptors ( Kang et al, 2019 ; Chamoun et al, 2020 ; Klein and Hultgren, 2020 ). The findings of the current study on the elevated levels of IL6 were in consistence with recent studies that also indicated that IL6 is a potent inducer of the progression of UTIs ( Becknell et al, 2015 ; Chamoun et al, 2020 ; Klein and Hultgren, 2020 ).…”

“…In response to pathogens of UTIs, IL6 is primarily secreted by the host, followed by the release into the serum, thereby inducing a transcriptional inflammatory response through IL6 receptors ( Kang et al, 2019 ; Chamoun et al, 2020 ; Klein and Hultgren, 2020 ). The findings of the current study on the elevated levels of IL6 were in consistence with recent studies that also indicated that IL6 is a potent inducer of the progression of UTIs ( Becknell et al, 2015 ; Chamoun et al, 2020 ; Klein and Hultgren, 2020 ). Therefore, the expressions of IL6 can be taken as the parameters to judge the effect on the development of UTIs.…”

“…As the leading cause of UTIs, Escherichia coli ( E. coli ) infections typically occur in the bladder (cystitis) and may ascend to the kidney, resulting in pyelonephritis ( Hozzari et al, 2020 ; Klein and Hultgren, 2020 ). In some severe cases, E. coli–related UTIs can progress to chronic renal failure or urosepsis, which may be fatal ( Chamoun et al, 2020 ; Klein and Hultgren, 2020 ). Virulence factors are the arsenal of bacteria, such as type P, type 1, type 3 fimbriae, etc.…”

Transcriptional alterations in bladder epithelial cells in response to infection with different morphological states of uropathogenic Escherichia coli

“…Interestingly, several pathways related to IL-17-signalling were among the top-scored pathways in all three morphological states. The importance of IL-17A for innate immunity in UTI is demonstrated by a defect in acute clearance of UPEC and higher bacterial burden in IL-17A-deficient mice 27 , 28 . Also, the known action of IL-17 in cell recruitment and immune regulation 29 imply that this cytokine is required to fine tune innate cellular defenses to UPEC in the bladder.…”

Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

“…[105][106] In addition, we measured IL-4, a cytokine produced in part by T h 2 (Type 2 T helper) CD4+ T cells, which induces an antibody-mediated response and IL-17, a cytokine that plays a protective role against E. coli infection. [107][108][109] We employed the vaccination schedule depicted in Figure 2C, and on day 42, re-stimulated splenocytes with CFT073 for each group. We measured TNF-α, IL-2, IFN-γ, IL-17, and IL-4 cytokine (Figure 4A-E) levels by ELISA and observed that mice immunized with CFT@ZIF had higher levels of all cytokines compared to CFT-Fixed treated mice following re-stimulation.…”