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T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive tr
Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocy
Chemokines constitute a large family of low-molecular-weight proteins (∼10 kDa in size), recognized primarily for their role in directing leukocyte migration under both homeostatic and inflammatory settings. The chemokine CCL25 displays a unique and highly restricted expression pattern compared with other chemokine family members. In the steady state, CCL25 is expressed at high levels primarily in
The mucosal lymphocyte integrin α(E)(CD103)β7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding α(E), localized it to chromosome 11, and generated integrin α(E)-deficient mice. In α(E)(-/-) mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of α(E)β7, to E-cadherin expressed on
Microbial attachment to mucosal surfaces is a first step in mucosal infection. Specific interactions between microbial surface ligands and host receptors influence the distribution of microbes in their sites of infection. Adhesion has often been regarded as a sufficient end point, explaining tissue tropism and bacterial persistence at mucosal sites. Adherence, however, is also a virulence factor t
Urine and serum interleukin (IL)-6 and IL-8 responses were higher in children with febrile urinary tract infection (n = 61) than in those with asymptomatic bacteriuria (n = 39). By univariate analysis, cytokine levels were related to age, sex, reflux, renal scarring, urine leukocytes, C- reactive protein (CRP), erythrocyte sedimentation rate (ESR), and bacterial properties (P fimbriae but not hemo
This study analysed the effects of immunoregulatory cytokines on uroepithelial cell cytokine responses. The A-498 human kidney cell line was treated with the interleukins IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, interferon gamma (IFN-α) and transforming growth factor beta (TGF-β1). Secreted IL-6 and IL-8 were quantitated by enzyme-linked immunoabsorbent assay (ELISA) and bioassay; IL-6 and IL-8 mRNA
Type 1 fimbriae are adhesion organelles expressed by many Gram-negative bacteria. They facilitate adherence to mucosal surfaces and inflammatory cells in vitro, but their contribution to virulence has not been defined. This study presents evidence that type 1 fimbriae increase the virulence of Escherichia coli for the urinary tract by promoting bacterial persistence and enhancing the inflammatory
Neutrophil influx to mucosal surfaces represents one of the earliest inflammatory responses to mucosal infection. We have been studying external interactions with urinary tract epithelial cells in an attempt to understand the molecular mechanisms behind this process. Uropathogenic Escherichia coli induced urinary tract epithelial cells to secrete the neutrophil chemoattractant interleukin-8 (IL-8)
During bacterial infections at mucosal sites, neutrophils migrate to the mucosa and cross the epithelial barrier. We have examined neutrophil migration across Escherichia coli-stimulated uroepithelial cell layers in an attempt to more fully understand this process. Stimulation of uroepithelial cells with E. coli or interleukin-1α (IL-1α) induced transepithelial neutrophil migration in a time- and
Localized at the border between the external environment and the internal tissue, epithelial cells are exposed to stimulants from two directions. Microorganisms in the lumen can activate the transcription of cytokine mRNA and cytokine secretion, and cytokines in the mucosal environment can modify endogenous and microbially induced epithelial cytokine responses. Epithelial cells thus actively parti
This study compared the cytokine production of uroepithelial cell lines in response to gram-negative bacteria and inflammatory cytokines. Human kidney (A498) and bladder (J82) epithelial cell lines were stimulated with either Escherichia coli Hu734, interleukin 1α (IL-1α), or tumor necrosis factor alpha (TNF-α). Supernatant samples were removed, and the RNA was extracted from cells at 0, 2, 6, and
Epithelial cell lines produce the cytokines IL-1α, IL-6 and IL-8 when stimulated with Escherichia coli. The cytokine response is enhanced by P fimbriae. The epithelial cell lines also respond to stimulation with other cytokines. These in vitro findings were confirmed in vivo in patients with E. coli infection who secreted IL-6 and IL-8 into the urine. The observations suggest that epithelial cells
This study compared the repertoire of cytokines produced by epithelial cell lines and human peripheral blood monocytes in response to Escherichia coli. The A-498 and J82 urinary tract epithelial cell lines and human peripheral blood monocytes were exposed to E. coli Hu734. The cytokine content of single cells was detected by indirect immunofluorescence using monoclonal antibodies to interleukin-1α
Urinary tract infections activate a mucosal inflammatory response, which includes cytokine secretion and neutrophil influx. The mechanisms involved in the neutrophil influx have not been identified. Interleukin-8, a potent chemoattractant for neutrophils, is produced by urinary tract epithelial cell lines in vitro. This study analyzed the human IL-8 response to deliberate Escherichia coli infectio
Trauma and infection activated a murine mucosal IL‐6 response in different ways: the IL‐6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL‐6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA‐insensitive IL‐6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exp
Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We so
DNA methylation patterns change with age and can be used to derive an estimate of "epigenetic age," an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variab
