scholarly journals Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis

2017 ◽  
Vol 92 (6) ◽  
Author(s):  
Nina M. Martin ◽  
Diane E. Griffin
Keyword(s):  
Weight Loss ◽  
Virus Strain ◽  
Th17 Cells ◽  
Severe Disease ◽  
Interleukin 10 ◽  
Viral Clearance ◽  
Th1 Cells ◽  
Virus Clearance ◽  
Virulent Virus ◽  
Antiviral Antibody

ABSTRACTAlphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053–16058, 2014,https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10−/−mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCEAlphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.

scholarly journals Relative COVID-19 Viral Persistence and Antibody Kinetics

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 752
Author(s):  
Chung-Guei Huang ◽  
Avijit Dutta ◽  
Ching-Tai Huang ◽  
Pi-Yueh Chang ◽  
Mei-Jen Hsiao ◽  
...  
Keyword(s):  
Early Stage ◽  
Severe Disease ◽  
Serum Antibody ◽  
Viral Persistence ◽  
Viral Clearance ◽  
The Other ◽  
Cytokines And Chemokines ◽  
Virus Clearance ◽  
Antibody Kinetics ◽  
Deceased Patient

A total of 15 RT-PCR confirmed COVID-19 patients were admitted to our hospital during the in-itial outbreak in Taiwan. The average time of virus clearance was delayed in seven patients, 24.14 ± 4.33 days compared to 10.25 ± 0.56 days post-symptom onset (PSO) in the other eight pa-tients. There was strong antibody response in patients with viral persistence at the pharynx, with peak values of serum antibody 677.2 ± 217.8 vs. 76.70 ± 32.11 in patients with delayed versus rapid virus clearance. The patients with delayed viral clearance had excessive antibodies of compromised quality in an early stage with the delay in peak virus neutralization efficacy, 34.14 ± 7.15 versus 12.50 ± 2.35 days PSO in patients with rapid virus clearance. Weak antibody re-sponse of patients with rapid viral clearance was also effective, with substantial and comparable neutralization efficacy, 35.70 ± 8.78 versus 41.37 ± 11.49 of patients with delayed virus clearance. Human Cytokine 48-Plex Screening of the serial sera samples revealed elevated concentrations of proinflammatory cytokines and chemokines in a deceased patient with delayed virus clear-ance and severe disease. The levels were comparatively less in the other two patients who suf-fered from severe disease but eventually survived.

scholarly journals Incidence and Outcomes of Home Parenteral Nutrition in Patients With Crohn Disease in Olmsted County, Minnesota

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Zeinab Bakhshi ◽  
Siddhant Yadav ◽  
Bradley R Salonen ◽  
Sara L Bonnes ◽  
Jithinraj Edakkanambeth Varayil ◽  
...  
Keyword(s):  
Weight Loss ◽  
Parenteral Nutrition ◽  
Short Bowel Syndrome ◽  
Crohn Disease ◽  
Severe Disease ◽  
Bloodstream Infections ◽  
Home Parenteral Nutrition ◽  
Average Weight ◽  
Olmsted County ◽  
Short Bowel

Abstract Background We sought to estimate the incidence of home parenteral nutrition (HPN) use in a population-based cohort of patients with Crohn disease (CD), and to assess clinical outcomes and complications associated with HPN. Methods We used the Rochester Epidemiology Project (REP) to identify residents of Olmsted County, who were diagnosed with CD between 1970 and 2011, and required HPN. Results Fourteen out of 429 patients (3.3%) with CD received HPN (86% female). Eleven patients (79%) had moderate–severe CD and 12 patients (86%) had fistulizing disease. Thirteen patients (93%) underwent surgery, primarily due to obstruction. Among CD incidence cases, the cumulative incidence of HPN from the date of CD diagnosis was 0% at 1 year, 0.5% at 5 years, 0.8% at 10 years, and 2.4% at 20 years. Indications for HPN included short bowel syndrome in 64%, malnutrition in 29%, and bowel rest in 21%. The median duration of HPN was 2.5 years. There was an average weight gain of 1.2 kg at 6 months, an average weight loss of 1.4 kg at 1 year, and a further weight loss of 2.2 kg at 2 years from the start of HPN. Patients were hospitalized a mean of 5 times after the start of HPN, mainly due to catheter-related bloodstream infections and thrombosis. Conclusions Less than 4% of patients with CD need HPN. Most have moderate to severe disease with short bowel syndrome or malnutrition. Possible reasons for the patients’ weight loss could be noncompliance, and increased metabolic needs because of active disease.

scholarly journals The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

2021 ◽  
Author(s):  
Yongji Li ◽  
Wendi Yang ◽  
Feng Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Treatment Efficacy ◽  
Th17 Cells ◽  
Immune Cell ◽  
Disease Risk ◽  
Th1 Cells ◽  
Clinical Role ◽  
Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

scholarly journals Development, Characterization, and Standardization of a Nose-Only Inhalation Exposure System for Exposure of Rabbits to Small-Particle Aerosols ContainingFrancisella tularensis

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Katherine J. O’Malley ◽  
Jennifer D. Bowling ◽  
Eileen M. Barry ◽  
Karsten R. O. Hazlett ◽  
Douglas S. Reed
Keyword(s):  
Weight Loss ◽  
Median Survival ◽  
Bacterial Culture ◽  
Severe Disease ◽  
Inhalation Exposure ◽  
Brain Heart Infusion ◽  
Survival Times ◽  
Exposure System ◽  
Content Type ◽  
Schu S4

ABSTRACTInhalation ofFrancisella tularensiscauses pneumonic tularemia in humans, a severe disease with a 30 to 60% mortality rate. The reproducible delivery of aerosolized virulent bacteria in relevant animal models is essential for evaluating medical countermeasures. Here we developed optimized protocols for infecting New Zealand White (NZW) rabbits with aerosols containingF. tularensis. We evaluated the relative humidity, aerosol exposure technique, and bacterial culture conditions to optimize the spray factor (SF), a central metric of aerosolization. This optimization reduced both inter- and intraday variability and was applicable to multiple isolates ofF. tularensis. Further improvements in the accuracy and precision of the inhaled pathogen dose were achieved through enhanced correlation of the bacterial culture optical density and the number of CFU. Plethysmograph data collected during exposures found that respiratory function varied considerably between rabbits, was not a function of weight, and did not improve with acclimation to the system. Live vaccine strain (LVS)-vaccinated rabbits were challenged via aerosol with human-virulentF. tularensisSCHU S4 that had been cultivated in either Mueller-Hinton broth (MHB) or brain heart infusion (BHI) broth. LVS-vaccinated animals challenged with SCHU S4 that had been cultivated in MHB experienced short febrile periods (median, 3.2 days), limited weight loss (<5%), and longer median survival times (∼18 days) that were significantly different from those for unvaccinated controls. In contrast, LVS-vaccinated rabbits challenged with SCHU S4 that had been cultivated in BHI experienced longer febrile periods (median, 5.5 days) and greater weight loss (>10%) than the unvaccinated controls and median survival times that were not significantly different from those for the unvaccinated controls. These studies highlight the importance of careful characterization and optimization of protocols for aerosol challenge with pathogenic agents.

scholarly journals Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells

2017 ◽  
Vol 198 (6) ◽  
pp. 2249-2259 ◽  
Author(s):  
Sharee A. Basdeo ◽  
Deborah Cluxton ◽  
Jamal Sulaimani ◽  
Barry Moran ◽  
Mary Canavan ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Th17 Cells ◽  
Th1 Cells

scholarly journals Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Noriko Morishima ◽  
Yukino Chiba ◽  
Junichiro Mizuguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Inflammatory Responses ◽  
Memory T Cells ◽  
Th1 Cells ◽  
Signal Transducers ◽  
Th Cell ◽  
Antigen Presenting

The interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN- production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)- production. IL-27 activates STAT1, as does IFN- and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.

Immune responses after influenza vaccination in patients of primary Sjögren’s syndrome

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 224-230
Author(s):  
Xingyu Zhou ◽  
Yisi Liu ◽  
Yuebo Jin ◽  
Yifan Wang ◽  
Miao Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccination ◽  
Th17 Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Th1 Cells ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

Abstract Objectives Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren’s Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination. Methods A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored. Results The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P&lt;0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P&lt;0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P&gt;0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS. Conclusion Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.

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