title: Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.
abstract: Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC) being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10) in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Duell
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Carey
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Dando
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D004927:Escherichia coli Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D001743:Urinary Bladder / Q000473:pathology*; D056689:Uropathogenic Escherichia coli / Q000502:physiology*; D019459:Urothelium / Q000473:pathology*
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D012333:RNA, Messenger; D016753:Interleukin-10