The collectins have been shown to play a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e.g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum but also in respiratory secretions; however, there has been very little study of the role of ficolins in viral infection. In this study we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid (BALF) bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or BALF reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogrates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, HA inhibition and viral aggregation caused by H-ficolin. Pandemic and mouse adapted strains of IAV are generally not inhibited by the collectins surfactant protein D (SP-D) or mannose binding lectin (MBL) due to paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV.
ObjectivesDendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS).MethodsFrequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment.ResultsWe observed that NTZ treatment was associated with a 25–50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation.ConclusionOur study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.
BackgroundVarious guidelines exist for female preventative screening tests and medical resident physician adherence to the United States Preventive Services Task Force (USPSTF) guidelines varies. National screening rates for breast cancer and osteoporosis have improved but they are still below the expected target.Material and methodsAmbulatory medical clinic records of female patients from the period July 2015 to December 2017 were reviewed for breast cancer and osteoporosis screening. Resident performance and commitment with regards to ordering the aforementioned screening tests according to the USPSTF guidelines were compared to the most recent national screening rates for mammograms and dual-energy X-ray absorptiometry (DXA) scans.ResultsOf the 1327 charts reviewed, 1025 was included in the study. Of the 545 mammograms performed, 93% of them were indicated according to the USPSTF guidelines (P < 0.0001, 95% CI: 125.9-342.0). A total of 480 mammograms were not ordered, of which 6% were indicated and 93.9% were not indicated. Out of a total of 107 DXA scans performed, 88.7% were correctly indicated (P < 0.0001, 95% CI: 37.11-132.9).ConclusionResident physician adherence to the USPSTF screening guidelines for breast cancer and DXA scans were higher than the national and state screening rates. Our well-structured educational project (strong faculty mentorship, resident to patient continuity of care and the reasonable resident-clinic load) resulted in higher screening rates.
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