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Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble Kupffer cells but are functionally distinct.

ABSTRACT: Due to a scarcity of immunocompetent animal models for viral hepatitis, little is known about the early innate immune responses in the liver. In various hepatotoxic models, both pro- and anti-inflammatory activities of recruited monocytes have been described. In this study, we compared the effect of liver inflammation induced by the Toll-like receptor 4 ligand lipopolysaccharide (LPS) with that of a persistent virus, lymphocytic choriomeningitis virus (LCMV) clone 13, on early innate intrahepatic immune responses in mice. LCMV infection induces a remarkable influx of inflammatory monocytes in the liver within 24 h, accompanied by increased transcript levels of several proinflammatory cytokines and chemokines in whole liver. Importantly, while a single LPS injection results in similar recruitment of inflammatory monocytes to the liver, the functional properties of the infiltrating cells are dramatically different in response to LPS versus LCMV infection. In fact, intrahepatic inflammatory monocytes are skewed toward a secretory phenotype with impaired phagocytosis in LCMV-induced liver inflammation but exhibit increased endocytic capacity after LPS challenge. In contrast, F4/80(high)-Kupffer cells retain their steady-state endocytic functions upon LCMV infection. Strikingly, the gene expression levels of inflammatory monocytes dramatically change upon LCMV exposure and resemble those of Kupffer cells. Since inflammatory monocytes outnumber Kupffer cells 24 h after LCMV infection, it is highly likely that inflammatory monocytes contribute to the intrahepatic inflammatory response during the early phase of infection. Our findings are instrumental in understanding the early immunological events during virus-induced liver disease and point toward inflammatory monocytes as potential target cells for future treatment options in viral hepatitis.Insights into how the immune system deals with hepatitis B virus (HBV) and HCV are scarce due to the lack of adequate animal model systems. This knowledge is, however, crucial to developing new antiviral strategies aimed at eradicating these chronic infections. We model virus-host interactions during the initial phase of liver inflammation 24 h after inoculating mice with LCMV. We show that infected Kupffer cells are rapidly outnumbered by infiltrating inflammatory monocytes, which secrete proinflammatory cytokines but are less phagocytic. Nevertheless, these recruited inflammatory monocytes start to resemble Kupffer cells on a transcript level. The specificity of these cellular changes for virus-induced liver inflammation is corroborated by demonstrating opposite functions of monocytes after LPS challenge. Overall, this demonstrates the enormous functional and genetic plasticity of infiltrating monocytes and identifies them as an important target cell for future treatment regimens.

SUBMITTER: Movita D

PROVIDER: S-EPMC4403491 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble Kupffer cells but are functionally distinct.

Movita Dowty D van de Garde Martijn D B MD Biesta Paula P Kreefft Kim K Haagmans Bart B Zuniga Elina E Herschke Florence F De Jonghe Sandra S Janssen Harry L A HL Gama Lucio L Boonstra Andre A Vanwolleghem Thomas T

Journal of virology 20150211 9

<h4>Unlabelled</h4>Due to a scarcity of immunocompetent animal models for viral hepatitis, little is known about the early innate immune responses in the liver. In various hepatotoxic models, both pro- and anti-inflammatory activities of recruited monocytes have been described. In this study, we compared the effect of liver inflammation induced by the Toll-like receptor 4 ligand lipopolysaccharide (LPS) with that of a persistent virus, lymphocytic choriomeningitis virus (LCMV) clone 13, on early ...[more]

PMID: 25673700

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Project description:BackgroundSurgical stabilization of rib fractures (SSRF) should be performed early after injury. Factors that influence timing remain unknown. Our objective was to identify inherent variables that allow for early identification and treatment. We hypothesized that certain demographic, injury, and logistical factors are associated with SSRF <24 hours from admission.MethodsRetrospective review from an urban level 1 trauma center (10/2010-8/2019). Patients were grouped as SSRF <24 hours from admission vs. ≥24 hours. Demographics, transfer from an outside hospital (OSH), timing documentation, injury descriptors, surgeon on-call, and operative surgeon were collected. SSRF for chronic non-union was excluded.ResultsData from 173 patients were analyzed. Eighty-five patients (49%) were in the <24 hours group and 88 (51%) were in the ≥24 hours group. Baseline demographics were similar between groups. Injury severity was significantly higher in the late group: increased Injury Severity Score (ISS; 16.5 vs. 21.0, P<0.01), lower Glasgow Coma Scale (GCS; 15 vs. 14, P<0.01), more rib fractures (7 vs. 9, P=0.01), and increased incidence of face (6% vs. 16%, P=0.03), spine (22% vs. 47%, P<0.01), and pelvis fractures (8% vs. 25%, P<0.01). Patients admitted on a Wednesday were more likely to undergo early SSRF as compared to other days of the week (P=0.01) There was also a shorter time from the decision to perform SSRF to the actual operation in the early group, as compared to the late group (13 vs. 44 hours, P<0.01). Fifty (28.9%) SSRF cases were performed by the on-call surgeon; this percentage did not differ in the early vs. late group (33% vs. 25%, P=0.25). Patients needing pelvic fixation were more likely to be in the late group. Patients transferred from an OSH for SSRF were more likely to be in the early group (29% vs. 10%, P<0.01). Finally, likelihood of early surgery increased with increasing study year.ConclusionsApproximately one-half of SSRF cases were performed within 24 hours of admission. Factors that influence surgery within 24 hours of admission appear related to overall injury severity and systems issues, including day of admission, transfer from another facility, additional urgent pelvic surgery, and institutional experience with SSRF. Surgeon availability did not drive this disparity.

Project description:Cochlear implantation is a surgical procedure, which is performed on severely hearing-impaired patients. Impedance field telemetry is commonly used to determine the integrity of the cochlear implant device during and after surgery. At the Department of Otolaryngology, Cheng Hsin General Hospital (Taipei, Taiwan), the cochlear implant devices are switched on within 24 hours of their implantation. In the present study, the impedance changes of Advanced Bionics™ cochlear implant devices were compared with previous studies and other devices. The aim was to confirm previous hypotheses and to explore other potential associated factors that could influence impedance following cochlear implantation. The current study included 12 patients who underwent cochlear implantation at Cheng Hsin General Hospital with Advanced Bionics cochlear implant devices. The cochlear devices were all switched on within 24 hours of their implantation. The impedance was measured and compared across all contact channels of the electrode, both intra-operatively and post-operatively. The intra-operative impedance was compared with the switch-on impedance (within 24 hours of the cochlear implantation); the impedance was notably increased for all contact channels at switch-on. Of the 16 channels examined, 4 channels had a significant increase in impedance between the intra-operative measurement and the switch-on measurement. To the best of our knowledge, the impedance of a cochlear implant device can be affected by the diameter of the electrode, the position of the electrode arrays in the scala tympani, sheath formation and fibrosis surrounding the electrode after implantation and electrical stimulation during or after surgery. When the results of the current study were compared with previous studies, it was found that the impedance changes were opposite to that of Cochlear™ implant devices. This may be explained by the position of the electrode arrays, sheath formation, the blow-out effect and differences in electrical stimulation.

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Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble Kupffer cells but are functionally distinct.

Publications

Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble Kupffer cells but are functionally distinct.

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