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      Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment

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          Abstract

          <p class="first" id="d15520438e182">Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to <i>Enterococcus faecalis</i> and uropathogenic <i>Escherichia coli</i> (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID <sub>90</sub> for infection of an undamaged urothelium with the same uropathogens. As the time of catheterization increased, however, colonization by the Gram-positive uropathogen <i>E</i>. <i>faecalis</i> was reduced, whereas catheterization created a sustained window of vulnerability to infection for Gram-negative UPEC over time. As CAUTI contributes to poorer patient outcomes and increased health care expenditures, we tested whether a single prophylactic antibiotic treatment, concurrent with catheterization, would prevent infection. We observed that antibiotic treatment protected against UPEC and <i>E</i>. <i>faecalis</i> bladder and catheter colonization as late as 6 hours after implantation. Thus, our study has revealed a simple, safe, and immediately employable intervention, with the potential to decrease one of the most costly hospital-incurred infections, thereby improving patient and health care economic outcome. </p><p class="first" id="d15520438e207">Bladder catheterization induces persistent sterile inflammation and increased susceptibility to bacterial colonization, which can be prevented by prophylactic antibiotic treatment concurrent with catheterization. </p>

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          Most cited references30

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          Points of control in inflammation.

          Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.
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            Langerhans cells arise from monocytes in vivo.

            Langerhans cells (LCs) are the only dendritic cells of the epidermis and constitute the first immunological barrier against pathogens and environmental insults. The factors regulating LC homeostasis remain elusive and the direct circulating LC precursor has not yet been identified in vivo. Here we report an absence of LCs in mice deficient in the receptor for colony-stimulating factor 1 (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have established that CSF-1 receptor-deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically recruited to the inflamed skin, proliferated locally and differentiated into LCs. These results identify Gr-1(hi) monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process.
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              Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo.

              We investigated the differentiation and trafficking of inflammatory monocytes that phagocytosed subcutaneously injected fluorescent microspheres. As expected, most of the monocytes became microsphere+ macrophages, which remained in subcutaneous tissue. However, about 25% of latex+ cells migrated to the T cell area of draining lymph nodes, where they expressed dendritic cell (DC)-restricted markers and high levels of costimulatory molecules. Microsphere-transporting cells were distinct from resident skin DCs, and this transport was reduced by more than 85% in monocyte-deficient osteopetrotic mice. Thus, a substantial minority of inflammatory monocytes carry phagocytosed particles to lymph nodes and differentiate into DCs.
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                Author and article information

                Journal
                JCI Insight
                American Society for Clinical Investigation
                2379-3708
                September 22 2016
                September 22 2016
                : 1
                : 15
                Article
                10.1172/jci.insight.88178
                5033754
                27699248
                326d8b59-23d5-40fb-9768-32dff2cacdfb
                © 2016
                History

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