Browsing by Subject "UTI"

Now showing 1 - 3 of 3
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    Environmental risk factors are associated with autoimmune hepatitis
    (Wiley, 2021) Lammert, Craig; Chalasani, Sai N.; Atkinson, Elizabeth J.; McCauley, Bryan M.; Lazaridis, Konstantinos N.; Medicine, School of Medicine
    Background: Failure of immunologic homeostasis and resultant hepatocyte destruction in autoimmune hepatitis (AIH) is likely the result of environmental triggers within a permissive genetic architecture. Aims: We aimed to identify risk factors associated with AIH in a well-phenotyped AIH cohort. Methods: We prospectively collected environmental questionnaires from 358 AIH cases and 563 healthy controls. Response frequencies were compared using logistic regression, adjusting for age at recruitment, sex and education. Results: AIH cases were more likely to ever have a urinary tract infection (UTI) (53.6% vs 33.9%, P < .001) and recurrent UTI (more than 1 per year) (23.5% vs 15.9%, P = .002) compared to controls. Female cases more frequently had ever used oral contraceptives (83.0% vs 73.7%, P = .006), fewer pregnancies (median = 1 vs 3, P < .001) and less often used hormone replacement therapy compared to controls (28.5% vs 60.1%, P < .001). Current smoking was more prevalent in cases (18.9% vs 7.4%, P = .022), yet no difference according to historical smoking behaviours was observed. Finally, cases were less likely to have history of mumps (32.4% vs 53.1%, P = .011) and rheumatic fever (1.1% vs 4.4%, P = .028), but reported higher vaccination frequency to chicken pox (38% vs 28.1%), measles (66.5% vs 39.3%), mumps (58.7% vs 34.6%), rubella (55.3% vs 32.7%), pertussis (59.8% vs 40.1%) and pneumococcus (47.2% VS 39.4%) (P < .002). Conclusions: Environmental factors are important in AIH pathogenesis. Replication of these findings and prospective examination may provide new insight into AIH onset and outcomes.
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    Protective vascular coagulation in response to bacterial infection of the kidney is regulated by bacterial lipid A and host CD147
    (Oxford, 2018-11-26) Schulz, Anette; Chuquimia, Olga D.; Antypas, Haris; Steiner, Svava E.; Sandoval, Ruben M.; Tanner, George A.; Molitoris, Bruce A.; Richter-Dahlfors, Agneta; Melican, Keira; Medicine, School of Medicine
    Bacterial infection of the kidney leads to a rapid cascade of host protective responses, many of which are still poorly understood. We have previously shown that following kidney infection with uropathogenicEscherichia coli (UPEC), vascular coagulation is quickly initiated in local perivascular capillaries that protects the host from progressing from a local infection to systemic sepsis. The signaling mechanisms behind this response have not however been described. In this study, we use a number ofin vitro andin vivo techniques, including intravital microscopy, to identify two previously unrecognized components influencing this protective coagulation response. The acylation state of the Lipid A of UPEC lipopolysaccharide (LPS) is shown to alter the kinetics of local coagulation onsetin vivo. We also identify epithelial CD147 as a potential host factor influencing infection-mediated coagulation. CD147 is expressed by renal proximal epithelial cells infected with UPEC, contingent to bacterial expression of the α-hemolysin toxin. The epithelial CD147 subsequently can activate tissue factor on endothelial cells, a primary step in the coagulation cascade. This study emphasizes the rapid, multifaceted response of the kidney tissue to bacterial infection and the interplay between host and pathogen during the early hours of renal infection.
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    The Role of IL-9 in Inflammatory Diseases: Allergic Asthma, Lung Cancer, and Urinary Tract Infections
    (2023-06) Pajulas, Abigail Lacanlale; Kaplan, Mark H.; Cook-Mills, Joan; Dent, Alexander; Zhou, Baohua
    Among the cytokines regulating immunity, interleukin 9 (IL-9) has gained considerable attention for its role in inflammation, immune tolerance, and tumor immunity. IL-9 has a broad array of functions and acts on multiple cell types to regulate immune responses. IL-9 receptor is expressed on both non-hematopoietic cells and hematopoietic cells in the innate and adaptive immune system. IL-9 demonstrates a remarkable degree of tissue-specific functionality that varies by tissue site and the context of the inflammatory milieu. In this dissertation, we investigate the biological activities of IL-9 and identify distinct IL-9-responsive cell type in the immune pathogenesis of disease models including allergic airway disease, lung cancer, and urinary tract infection. When examining airway hyperreactivity, we found IL-9-dependent mast cell function was critical. Using adoptive transfer models and newly generated mice with an inactivation of the Il9 gene restricted to T cells generated by CD4-cre/LoxP-mediated targeting, we demonstrate that T cell secreted IL-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration during allergic airway inflammation. In IL-9-mediated pro-tumor responses, interstitial macrophages, but not mast cells, respond to T cell IL-9 to enhance B16 metastatic tumor growth. In the context of urinary tract infection, IL-9 contributes to protection against E. coli bladder infection potentially by enhancing CCL20 production in epithelial cells to recruit macrophages and neutrophils. Altogether, IL-9 can exert cell type-specific effects that identify its roles in immunity and disease. This perspective will be important in defining the diseases where targeting IL-9 as a therapeutic strategy would be beneficial, and where it has the potential to complicate clinical outcomes.