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Molecular Immunology
Pergamon Press
Molecular Immunology

Pergamon Press

0161-5890

Molecular Immunology/Journal Molecular ImmunologySCIISTP
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    A tribute to Nilabh Shastri and a special issue on antigen processing and presentation in Paris (APP10, Paris 2019)

    Hosmalin, AnneManoury, Benedicte
    2页
    查看更多>>摘要：The Special Issue is dedicated to the 10th Antigen Processing and Presentation Workshop, which took place at Institut Cochin in Paris from May 28th to June 2nd, 2019. It contains several reviews or original articles from contributors to this workshop. It is also a vibrant Tribute to Nilabh Shastri, founder of the APP Workshops, who untimely passed away in 2021 and is deeply missed by his colleagues and friends.
      原文链接:
    • NSTL
    • Elsevier

    Functional reconstitution of the MERS CoV receptor binding motif

    Weiss-Ottolenghi, YaelRoitburd-Berman, AnnaGraham, Barney S.Dimitrov, Dimiter S....
    14页
    查看更多>>摘要：In the early 1960's the first human coronaviruses (designated 229E and OC43) were identified as etiologic agents of the common cold, to be followed by the subsequent isolation of three more human coronaviruses similarly associated with cold-like diseases. In contrast to these "mild" coronaviruses, over the last 20 years there have been three independent events of emergence of pandemic severe and acute life-threatening respiratory diseases caused by three novel beta-coronaviruses, SARS CoV, MERS CoV and most recently SARS CoV2. Whereas the first SARS CoV appeared in November 2002 and spontaneously disappeared by the summer of 2003, MERS CoV has continued persistently to spill over to humans via an intermediary camel vector, causing tens of cases annually. Although human-to-human transmission is rare, the fatality rate of MERS CoV disease is remarkably higher than 30%. COVID-19 however, is fortunately much less fatal, despite that its etiologic agent, SARS CoV2, is tremendously infectious, particularly with the recent evolution of the Omicron variants of concern (BA.1 and BA.2). Of note, MERS CoV prevalence in camel populations in Africa and the Middle East is extremely high. Moreover, MERS CoV and SARS CoV2 co-exist in the Middle East and especially in Saudi Arabia and the UAE, where sporadic incidences of co-infection have already been reported. Co-infection, either due to reverse spill -over of SARS CoV2 to camels or in double infected humans could lead to recombination between the two vi-ruses, rendering either SARS CoV2 more lethal or MERS CoV more transmittable. In an attempt to prepare for what could develop into a catastrophic event, we have focused on developing a novel epitope-based immunogen for MERS CoV. Implementing combinatorial phage-display conformer libraries, the Receptor Binding Motif (RBM) of the MERS CoV Spike protein has been successfully reconstituted and shown to be recognized by a panel of seven neutralizing monoclonal antibodies.
      原文链接:
    • NSTL
    • Elsevier

    Stratification of COVID-19 patients based on quantitative immune-related gene expression in whole blood

    Persson, JosefineAndersson, Bjornvan Veen, SuzanneHaks, Marielle C....
    10页
    查看更多>>摘要：The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes mild symptoms in the majority of infected individuals, yet in some cases it leads to a life-threatening condition. Determination of early predictive biomarkers enabling risk stratification for coronavirus disease 2019 (COVID-19) patients can inform treatment and intervention strategies. Herein, we analyzed whole blood samples obtained from individuals infected with SARS-CoV-2, varying from mild to critical symptoms, approximately one week after symptom onset. In order to identify blood-specific markers of disease severity status, a targeted expression analysis of 143 immune-related genes was carried out by dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA). The clinically well-defined subgroups of COVID-19 patients were compared with healthy controls. The transcriptional profile of the critically ill patients clearly separated from that of healthy individuals. Moreover, the number of differentially expressed genes increased by severity of COVID-19. It was also found that critically ill patients can be distinguished by reduced peripheral blood expression of several genes, which most likely reflects the lower lymphocyte counts. There was a notable predominance of IFN-associated gene expression in all subgroups of COVID-19, which was most profound in critically ill patients. Interestingly, the gene encoding one of the main TNF-receptors, TNFRS1A, had selectively lower expression in mild COVID-19 cases. This report provides added value in understanding COVID-19 disease, and shows potential of determining early immune transcript signatures in the blood of patients with different disease severity. These results can guide further explorations to uncover mechanisms underlying immunity and immunopathology in COVID-19.
      原文链接:
    • NSTL
    • Elsevier

    The genetics behind inflammasome regulation

    Yamada, Suemy MelimPontillo, Alessandra
    16页
    查看更多>>摘要：The inflammasome is a cytosolic multiproteic complex that promotes proinflammatory events through the release of the cytokines IL-1 beta and IL-18, and in some context by the induction of a lytic cell death called pyroptosis, in response to damage, infections, or changes in the homeostasis. Due to the powerful inflammatory effect, there are several regulatory mechanisms that are essential to modulate or limit the activation of the inflammasome. When these mechanisms fail, the deregulation of the complex leads or contributes to the development of a plethora of diseases characterized by constitutive and/or chronic inflammation, such as autoinflammatory, autoimmune, cardiovascular, neurodegenerative, and metabolic diseases, cancer, or even severe complications of infectious diseases.Either environmental or genetic factors may affect the threshold and/or the level of inflammasome activation, such as hyperglycemia, hyperuricemia, auto-antibodies, unfolded proteins and fibrils, or individual genetic variants in genes coding for inflammasome receptors or effector molecules, and also in regulators.While the genetics of inflammasome itself has been elsewhere characterized and also recently reviewed by our group, less is known about how genetic variants in regulatory molecules could affect inflammatory diseases. Therefore in this work, we selected a group of known or possible regulators of the inflammasome, and through the review of genetic association studies we tried to depict the contribution of these regulators in the devel-opment of multifactorial diseases.
      原文链接:
    • NSTL
    • Elsevier

    Complement Factor H related protein 1 and immune inflammatory disorders

    Zong, JingSi, ShaoyanLi, Xiangru
    7页
    查看更多>>摘要：Human complement Factor H-related protein 1 (FHR-1) is one of complement Factor H-related proteins (FHRs) and plays an important role in innate immunity. In particular, FHR-1 promotes complement activation by competing with Factor H (FH) for ligands on different surfaces or directly binding to C3b and native C3. Paradoxically, FHR-1 restrains complement activation by inhibiting C5 convertase and terminal complement complex (TCC) formation, and in vitro assays showed that the physiological concentration of FHR-1 had no obvious C3 and C5 regulatory activity. FHR-1 also plays a role in the inflammatory process. MDA-bound FHR-1 promotes inflammatory cytokine release from monocytes in a complement-independent manner. However, its deficiency increases TNF alpha, IL18, IL6, and IL10 secretion from monocytes stimulated with LPS and R484. These contradictory effects of FHR-1 in innate immunity indicate that FHR-1 may function differently in different scenarios. Dysregulation of innate immunity due to frequent CFHR1 variations is associated with various immune inflammatory disorders. Mutations in the C-terminus of FHR-1 that increase its similarity with FH are associated with atypical haemolytic uraemia syndrome (aHUS). In contrast, mutations in the N-terminus that increase the multimerization of FHRs are associated with C3 glomerulopathy (C3G). Changes in FHR-1 concentration have been observed in other diseases. The different functions of the C-terminus and N-terminus of FHR-1 and the distinct function of FHR-1 under various conditions may explain the association of CFHR1 variations with different diseases. Here, we summarized the recent progress on FHR-1 and dissected its role in various immune inflammatory disorders, helping to comprehend and further explore the disease pathogenesis.
      原文链接:
    • NSTL
    • Elsevier

    Viral resistance to VRC01-like antibodies with mutations in loop D and V5 from an HIV-1 B' subtype infected individual with broadly neutralization activity

    Zhang, DaiLiu, ZhenWang, WeiChen, Ming-Xin...
    9页
    查看更多>>摘要：Recently we identified the VRC01-like antibody DRVIA7(A7) from an HIV-1 B' subtype-infected individual (DRVI01) with broad neutralization activity, and almost all viruses from the individual were resistant to both VRC01 and A7 lineage antibodies. Here, we identified and characterized a panel of HIV-1 variants with resistance to VRC01 and A7 using site-directed mutagenesis and swapping amino acid fragments of gp120. Site-directed mutagenesis revealed that E279D/R282K/N460A/T464N of gp120 from DRVI01 produced VRC01-susceptible variants. Multiple mutations significantly increased the neutralization sensitivity to VRC01. Residues N464 located at the tip of the V5 loop were considered irrelevant to the neutralization of VRC01. For DRVI01-derived viruses, the single N464T change fully produced VRC01-resistant variants; conversely, a single T464N mutation generated VRC01-susceptible variants. Alanine scanning revealed that the N464 residue plays a vital role in binding with VRC01. Neutralizing assays against A7 lineage antibodies showed that DRVI01-derived viruses with multiple mutations could be neutralized by A7 lineage antibodies with different neutralizing breadths. Combining the changes in loops D and V5 produced variants that were totally sensitive variants to A7 lineage antibodies.
      原文链接:
    • NSTL
    • Elsevier

    Three patterns of sensitization to mugwort, timothy, birch and their major allergen components revealed by Latent class analysis

    Wu, LitingHou, XiangqingLuo, WentingHu, Haisheng...
    8页
    查看更多>>摘要：Background: Mugwort, timothy, and birch are commonly spread pollen allergens across China. Although several studies have described the rates of sensitization to mugwort, timothy, and birch in China, most of them just on specific whole-allergen extracts but little was known about the co-sensitization characteristics of its allergen components. This study aimed to explore the patterns of sensitization to mugwort, timothy, birch, and their major allergen components.Method: Serum specific IgE (sIgE) levels of allergen components of mugwort, timothy, birch, and cross-reactive carbohydrate determinants (CCD) were detected in 160 patients whose serum showed positive results to at least one of mugwort, timothy, and birch allergens via EUROBlotMaster system. Skin prick testing was utilized to assess the allergic reaction of grass, weed, and tree allergens. Latent class analysis was used to identify under-lying patterns of sensitization to a series of allergen components and their corresponding extracts.Results: 88.8% of patients with allergic rhinitis and/or asthma were positive for mugwort-sIgE, 30% for timothy-sIgE, and 32.5% for birch-sIgE. By using the LCA model, three sensitization patterns as "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized", "Timothy, mugwort, and CCD co-sensitized", "Mugwort and Art v 1 co-sensitized" were revealed based on optimal statistical fit in this study. Compared with other clusters, participants in "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized" pattern were associated with higher sensitization rates of common grass and tree pollens allergen. The spearman's coefficient between CCD and timothy was larger than the corresponding values of CCD with mugwort or birch.Conclusion: CCD and profilin, as minor allergens in pollens, were associated with other pollen sIgE false positives presumably due to cross-reactivity. Patients sensitized with profilin had a significantly higher risk of sensitization to other pollens.
      原文链接:
    • NSTL
    • Elsevier

    Clonal expansion and markers of directed mutation of IGHV4-34 B cells in plasmablasts during Kawasaki disease

    Baron, SarahHoffman, JonathonHicar, Mark D.Chang, Arthur J....
    11页
    查看更多>>摘要：Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. A variety of pathophysiologic responses have been proposed, including direct invasion of the coronary arteries, a superantigen response, and a post-infectious autoimmune phenomenon. A role for B cell responses during KD are supported by numerous findings including B cell specific markers identified in genome wide association studies. We have recently published data showing children with KD have similar plasmablast (PB) responses to children with infections. Since during other infections, cells expressing antibodies against the preceding infection are enriched in PBs, we sought to explore the specific antibodies encoded by PBs during KD. In one child we see a massive expansion in IGHV4-34 utilizing antibodies, which has been associated with autoimmunity in the past. We further explored this expansion of IGHV4-34 utilization during the peripheral PB rise with next generation sequencing (NGS) analysis and utilizing newer techniques of chromium chip single cell separation (10x Genomics (R)). We also utilized peptide array screening to attempt to identify an antigen to the most prolific clones.
      原文链接:
    • NSTL
    • Elsevier

    Use of sulforaphane in COVID-19: Clinical trials are needed

    Kow, Chia SiangRamachandram, Dinesh SangarranHasan, Syed Shahzad
    2页
    查看更多>>摘要：We read with interest the narrative review authored by Kiser et al. (2021), which discussed extensively the antioxidant effect and anti-inflammatory effect of sulforaphane, a dietary supplement found in high amounts in cruciferous vegetables that ais orally accessible and well-tolerated. Notably, in their review, the authors also discussed the potential use of sulforaphane in patients with coronavirus disease 2019 (COVID-19). Sulforaphane mediates the inhibitory effect on NLRP3 inflammasome activation and we believe that this could be the main mechanism where sulforaphane is useful for patients with COVID-19.
      原文链接:
    • NSTL
    • Elsevier

    The liver metabolic features of Mogroside V compared to Siraitia grosvenorii fruit extract in allergic pneumonia mice

    Liu, YisaWang, JuanDou, TongZhou, Luwei...
    8页
    查看更多>>摘要：Background: For a long time, Siraitia grosvenorii fruit extract (SGFE) and its dominant compounds, mogroside V (MV) were both reported to have therapeutic effects on allergic pneumonia, while previous studies only stay on phenotype and mechanism of the two active ingredients, hardly have any studies compared the two ingredients on the effect of liver metabolic, and revealed the relationship between mechanism and liver metabolism. Objective: Here we elucidated and compared the curative mechanisms of SGFE and MV on allergic pneumonia through liver metabolomics. Methods: We established allergic pneumonia mice using ovalbumin, then treated the mice with SGFE, MV and positive drug of Suhuang Zhike Jiaonang. The effects of the drugs were evaluated by detecting inflammatory cytokines, pathological examination and liver oxidative stress biomarkers. We explored the metabolic features between SGFE and MV through liver metabolomics consequently. Results: At phenotype, we confirmed that MV and SGFE both inhibited the expression of inflammatory cytokines including interleukins-5 (IL-5), IL-13, IL-17 and OVA-induced immunoglobulin E, which can also relieve inflammatory cells infiltration and mesenchymal thickening in lung tissue compared with positive drug. In addition, both of them can alleviate oxidative stress damage in liver, while MV showed a superior effect than SGFE. In metabolomic analysis, the two ingredients were found to ameliorate inflammatory and oxidative reaction mainly in controlling pathways of Riboflavin metabolism and Glutathione metabolism. While SGFE were found to control other metabolic pathways such as Phenylalanine metabolism, Sphingolipid metabolism, Glycerollipid metabolism, Glycine, serine and threonine metabolism and Arginine and proline metabolism. Conclusion: From the results we can infer that the minor ingredients except MV in SGFE contribute poor function to the treatment of allergic pneumonia and MV may be the main functional constituent that relieve allergic pneumonia in SGFE. This study will be beneficial to figuring out a systematic theory of Siraitia grosvenorii active ingredients and proposing a guidance for pharmacology development.
      原文链接:
    • NSTL
    • Elsevier