Top 6 Biorxiv Papers Today in Immunology


2.028 Mikeys
#1. Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque responses
Silvia Oggero, Monica de Gaetano, Simone Marcone, Mary Barry, Trinidad Montero-Melendez, Dianne Cooper, Lucy Victoria Norling, Eoin Brennan, Catherine Godson, Mauro Perretti
In atherosclerosis, a chronic disease characterized by lipid accumulation, fibrosis and vascular inflammation, extracellular vesicles (EVs) are emerging as key players in different stages of disease development. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF-α are both CD14+ and CD41+. Tempering platelet activation with Iloprost™ impacted the quality and quantity of EV produced. Proteomics of EVs from cells activated with TNF-α alone or in presence Iloprost™ revealed distinct proteome, with selective hits like gelsolin. EVs from TNF-α stimulated monocytes augmented release of cytokines, and modulated more than 500 proteins by proteomics, when added to human atherosclerotic plaques. In contrast, EVs generated by TNF-α and Iloprost™ produced minimal plaque activation. In conclusion, attenuating platelet activation has an effect on EV composition released from monocyte/platelet aggregates with downstream modulation of their pro-inflammatory actions and contribution to the...
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biorxivpreprint: Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque responses https://t.co/gqEK09DeQm #bioRxiv
biorxiv_immuno: Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque responses https://t.co/iuYhzg8TSp #biorxiv_immuno
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Authors: 10
Total Words: 0
Unqiue Words: 0

2.0 Mikeys
#2. The Consequences of Egg Adaptation in the H3N2 Component to the Immunogenicity of Live Attenuated Influenza Vaccine
Daniel H. Goldhill, Benjamin Lindsey, Ruthiran Kugathasan, Zandra Felix Garza, Ya Jankey Jagne, Hadijatou Jane Sallah, Gabriel Goderski, Sophie van Tol, Katja Höschler, Adam Meijer, Wendy S. Barclay, Thushan de Silva
Adaptation in egg-passaged vaccine strains may cause reduced vaccine effectiveness due to altered antigenicity of the influenza haemagglutinin. We tested whether egg adaptation modified serum and mucosal antibody responses to the A(H3N2) component in the Live Attenuated Influenza Vaccine (LAIV). Twice as many children seroconverted to an egg-adapted H3N2 than the equivalent wildtype strain. Seroconversion to the wildtype strain was greater in children seronegative pre-LAIV, whereas higher mucosal IgA responses to wildtype antigen were observed if seropositive prior to vaccination. Sequencing of virus from nasopharyngeal swabs from 7 days post-LAIV showed low sequence diversity and no reversion of egg-adaptive mutations.
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Code for analyzing next-gen sequencing data from LAIV from the Gambia.

Repository: GambiaLAIV
User: Flu1
Language: R
Stargazers: 0
Subscribers: 1
Forks: 0
Open Issues: 0
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Sample Sizes : [118, 126, 100, 114]
Authors: 12
Total Words: 4385
Unqiue Words: 1732

1.995 Mikeys
#3. In-silico immune cell deconvolution of the airway proteomes of infants with pneumonia reveals a link between reduced airway eosinophils and an increased risk of mortality
Charles J Sande, Jacqueline M Waeni, James M Njunge, Martin M Mutunga, Elijah T Gicheru, Nelson K Kibinge, Agnes Gwela
Rationale: Pneumonia is a leading cause of mortality in infants and young children. The immune responses in the airway that are associated with mortality are poorly understood. Studies of the cellular immunology of the infant airway have traditionally been hindered by the limited sample volumes available from the young, frail children who are admitted to hospital with pneumonia. This is further compounded by the relatively low frequencies of certain immune cell phenotypes that are thought to be critical to the clinical outcome of infection. To address this, we developed a novel in-silico deconvolution method for inferring the frequencies of immune cell phenotypes in the airway of children with different survival outcomes using proteomic data. Methods: Using high-resolution mass spectrometry, we identified > 1,000 proteins expressed in the airways of children who were admitted to hospital with clinical pneumonia. 61 of these children were discharged from hospital and survived for more than 365 days after discharge, while 19 died...
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1.989 Mikeys
#4. HLA class II polymorphism influences the immune response to protective antigen and susceptibility to Bacillus anthracis
Daniel M Altmann, Stephanie Ascough, Rebecca Ingram, Karen Chu, Stephen Moore, Theresa Gallagher, Hugh Dyson, Mehmet Doganay, Gökhan Metan, Yusuf Ozkul, Les Baillie, E. Diane Williamson, John Robinson, Bernard Maillere, Rosemary Boyton
Abstract The causative agent of anthrax, Bacillus anthracis , evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were...
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1.975 Mikeys
#5. Origin and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.
Calum C Bain, Douglas A Gibson, Nicholas J Steers, Katerina Boufea, Pieter A Louwe, Catherine Doherty, Victor Huici, Rebecca Gentek, Marlene Magalhaes-Pinto, Marc Bajenoff, Cecile Benezech, David Dockrell, Philippa TK Saunders, Nizar Batadar, Stephen J Jenkins
Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the aetiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behaviour is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single cell RNAseq revealed striking dimorphisms in gene expression between male and female peritoneal macrophages that was in part explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with...
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1.946 Mikeys
#6. Single-cell immune repertoire tracing identifies rituximab refractory B cells that emerge during relapse
Roy Jiang, Miriam L. Fichtner, Kenneth B. Hoehn, Panos Stathopoulos, Richard J. Nowak, Steven Kleinstein, Kevin C. OConnor
Rituximab, an anti-CD20 B cell-depleting therapy, is indicated to treat a growing number of autoimmune disorders. However, disease relapses can occur when the B cell compartment is re-established after treatment. To explore the mechanism of relapse, we studied patients with muscle-specific kinase (MuSK) myasthenia gravis (MG), a paradigm for B cell-mediated autoimmune diseases in which pathology is directly associated with autoantibody production. Whether the failed depletion of specific clones leads to the persistence of autoantibody producing B cell subsets has yet to be elucidated. Here we show that rituximab (RTX) therapy is not fully effective at eliminating disease-associated B cells and provide a mechanistic understanding of relapse. We carried out single-cell transcriptional and B cell receptor (BCR) profiling on longitudinal B cell samples from the peripheral blood of MuSK MG patients who relapsed after rituximab therapy. Computational analysis of these data identified individual B cells that were refractory to rituximab...
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