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Background: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection.Methods: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection.Results: Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14-/- HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production.Conclusions: We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication. [ABSTRACT FROM AUTHOR]

Background: Bacterial resistance to antibiotics is an increasingly threatening consequence of antimicrobial exposure for many decades now. In urinary tract infections (UTIs), antibiotic prophylaxis (AP) increases bacterial resistance. We studied the resistance patterns of positive urinary cultures in spina bifida children on clean intermittent catheterization, both continuing and stopping AP.Methods: In a cohort of 176 spina bifida patients, 88 continued and 88 stopped using AP. During 18 months, a fortnightly catheterized urine sample for bacterial pathogens was cultured. UTIs and significant bacteriuria (SBU) were defined as a positive culture with a single species of bacteria, respectively with and without clinical symptoms and leukocyturia. We compared the percentage of resistance to commonly used antibiotics in the isolated bacteria in both groups.Results: In a total of 4917 cultures, 713 (14.5%) had a positive monoculture, 54.3% of which were Escherichia coli. In the group stopping AP, the resistance percentage to antibiotics in UTI / SBU bacteria was lower than in the group remaining on AP, even when excluding the administered prophylaxis.Conclusion: Stopping antibiotic prophylaxis for urinary tract infections is associated with reduced bacterial resistance to antibiotics in children with spina bifida.Trial Registration: ISRCTN ISRCTN56278131 . Registered 20 December 2005. [ABSTRACT FROM AUTHOR]

Abstract Cystic fibrosis (CF) patients are colonized with a multitude of bacteria and fungi. From respiratory samples of two CF patients in our institute, a difficult to identify yeast was isolated repeatedly. This yeast was eventually identified as Cutaneotrichosporon (Cryptococcus) cyanovorans by internal transcribed spacer (ITS) and ribosomal large subunit (LSU) sequencing. C. cyanovorans is a basidiomycetous yeast originally reported as environmental isolate from South African soil and has not been described before as clinical isolate from CF patients. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "The Influence of Antibiotic Prophylaxis on Bacterial Resistance in Urinary Tract Infections in Children with Spina Bifida" which appeared in the 2017 issue.

Human monocytes express on their plasma membrane relatively large number of CD14 molecules, known to play a crucial role in the lipopolisaccharide (LPS)-mediated cellular activation. Indirect data (J. Biol. Chem. 270 (1995) 9904) suggest that not all of these CD14 molecules participate in LPS-signaling, but the importance of these spare receptors and the exact number of CD14 involved in activation upon different LPS-stimuli is not known. Using different concentrations of a blocking anti-CD14 monoclonal antibody (mAb 60bca) we created monocytes with graded amounts of CD14. The exact number of occupied and free receptors was quantitated by flow cytometry and special mAb-labeled standard beads. The number of free CD14 molecules per monocyte in the presence of 10, 3.33, 0.73, 0.25 and 0.041 μg/ml mAb was 0, 13 100, 49 300, 97 700 and 165 900. Stimulation of these partially blocked monocytes with 0.1, 1, 10 and 100 ng/ml ReLPS in the presence of 3% human serum revealed that already 13 100 and 97 700 CD14 molecules provided a maximal Tumor necrosis factor α (TNFα) mRNA response using 100 and 10 ng/ml ReLPS, while the activation totally depended on the number of available CD14 molecules in the case of 1 and 0.1 ng/ml ReLPS. Our data imply that the number of CD14 molecules available for LPS-binding influence the cellular response. In the presence of higher concentrations of LPS only fractions of CD14 participate in the cell activation, while the presence of the spare receptors enhance the sensitivity against lower LPS amounts. [Copyright &y& Elsevier]