{"title":"Proteome-wide Epitope Prediction: Leveraging Bioinformatic Technologies in Rational Vaccine Design","authors":"Lindsay M. W. Piel, S. White","doi":"10.33696/immunology.3.120","DOIUrl":"https://doi.org/10.33696/immunology.3.120","url":null,"abstract":"Vaccine development began in the 1790’s when Edward Jenner used cowpox to confer protection against the smallpox virus [1]. The field of vaccinology has greatly expanded since then, wherein vaccination has been a valuable tool in the decline of many diseases [1,2]. While Jenner’s use of cowpox shares attributes to a live-attenuated vaccine, there are alternate methods of vaccination, which include subunit, conjugate, mRNA, viral vector, and toxoid vaccines [2-4]. Development of these methods was facilitated through greater understanding of the immune response, elucidation of both host and pathogen genetic diversity, and advancement of laboratory techniques [1-3]. The most recent notable advancement in vaccine production was the development of a nucleic acid vaccine to combat the SARS-CoV-2 virus [1]. While advancement in vaccine methodology can be readily seen, many subunit-based vaccines end up generating a predominantly B-cell driven response [1,5].","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48621885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Monk, Amber L. Hutchinson, Jamie L. A. Martin, L. Robinson
{"title":"Using Immune Cell/Adipocyte Co-Culture Models to Identify Inflammatory Paracrine Signaling Mechanisms: A Process Attenuated by Long-Chain N-3 Polyunsaturated Fatty Acids","authors":"J. Monk, Amber L. Hutchinson, Jamie L. A. Martin, L. Robinson","doi":"10.33696/immunology.3.114","DOIUrl":"https://doi.org/10.33696/immunology.3.114","url":null,"abstract":"This invited Commentary is on the methods paper entitled “Studying adipocyte and immune cell cross talk using a co-culture system” in Immunometabolism: Methods and Protocols [1]. Co-culturing individual immune cell populations (as primary cells or cell lines) with adipocytes represents a model system to study the paracrine interactions (or cross-talk) between cell types that can impact adipose tissue (AT) function. This is particularly relevant in obese AT, wherein paracrine interactions between cell types promotes the secretion of inflammatory mediators that contribute to increased local (i.e. within the AT) and systemic low-grade inflammation and metabolic dysfunction, including insulin resistance (IR) [2-5].","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44603198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Guanylate Binding Proteins promote anti-Leishmania Host Cell Defense","authors":"A. Haldar","doi":"10.33696/immunology.3.113","DOIUrl":"https://doi.org/10.33696/immunology.3.113","url":null,"abstract":"Leishmania donovani is an obligatory intracellular protozoa pathogen that transmits by sand flies to mammalian hosts. L. donovani is the causative agent of the disease Visceral Leishmaniasis (VL), also known as Kala-azar, which causes hepatosplenomegaly i.e., enlargement of the spleen and liver in patients. The VL is regarded as one of the most devastating neglected infectious diseases in tropical and sub-tropical regions and can be fatal if the patients left untreated [1]. Professional phagocytic cells (e.g., macrophages, dendritic cells, neutrophils) are considered to be the most important host cells for L. donovani for its survival and replication [2-4]. However, several in vitro and in vivo studies have shown that non-phagocytic cell types like epithelial cells and fibroblasts [5-7] endocytose L. donovani. Despite the significance of these findings, little attempt has been made to address the questions: 1) How these non-phagocytic cells restrict parasite growth? 2) Does it depend on an interferon-induced pathway? 3) If not, then how do nonphagocytic cells control this pathogen? In a recent study, we discovered that non-phagocytic cells have intrinsic properties that limit L. donovani growth even in the absence of interferon-gamma (IFNγ) stimulation via an autophagy mediated non-canonical pathway [6].","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45485181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Priori, F. Giardina, F. Spinelli, C. Iannuccelli, F. Conti
{"title":"Resilience in Rheumatic and Musculoskeletal Diseases","authors":"R. Priori, F. Giardina, F. Spinelli, C. Iannuccelli, F. Conti","doi":"10.33696/immunology.3.117","DOIUrl":"https://doi.org/10.33696/immunology.3.117","url":null,"abstract":"Along the last decade, likewise in other fields, the concept of resilience has been gaining relevance in medicine and psychology where, although many different definitions have been proposed, it can be briefly described as the skill to positively cope with stressful life events [1]. Chronic conditions such as rheumatic and musculoskeletal diseases (RMD) have a great impact on the quality of life, and resilience can help to withstand RMD associated pain and disability [2]. Being influenced by a wide spectrum of variables such as age, gender, culture, sociological context, education, and personal experiences, resilience can be either an innate ability or it can be acquired through a dynamic process [1,3]. Some evidence suggests that patients with RMD may have more effective coping strategies in response to stressful life events due to adaptive responses to the chronicity of their condition [3,4] and, consequently, they might deal better with unexpected stressful experiences. In this light, unsurprisingly, patients with inflammatory arthritis are more resilient than the general population towards unpredictable stressful situations such as the ongoing COVID-19 pandemic [5]. However, interventions able to strengthen the active process of resilience may reasonably improve the outcomes of RMD [6].","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"37 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41282567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COVID-19 Clinical Outcomes and Vaccine Efficacy among Patients with Hematologic Malignancies","authors":"Sarah Gillaspie, M. Hoffmann","doi":"10.33696/immunology.3.112","DOIUrl":"https://doi.org/10.33696/immunology.3.112","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) pandemic places the treating hematologist in a quandary: how best to protect patients with hematologic malignancies from potentially deadly COVID-19 infection while also providing the best therapy for their disease and maximizing opportunities for cure. Cancer patients as a whole trend toward more severe infection and increased mortality from COVID-19 infection. This burden, however, is not equally distributed among all cancer patients and outcomes are particularly poor in those with hematologic malignancies [1]. Lymphodepleting treatments have a profound effect on COVID outcomes; we have recently reported that despite proper and even prolonged quarantine after asymptomatic positive screening test for COVID-19, the initiation of rituximab-based chemotherapy resulted in a delayed respiratory failure in three lymphoma patients [2]. In addition to more severe infection and increased mortality, immunocompromised patients shed virus and remain infectious for far longer than the general population, frequently for several months or longer [3,4]. Finally, to add insult to injury, patients with hematologic malignancies have worse clinical and laboratory responses to vaccines, compromising their ability to be protected against infection and severe disease [5,6]. Prolonged viral shedding, decreased ability to form a durable immune response to vaccination or infection, and subsequent increased probability for severe infection pose a problem for those needing treatment due to progressive disease. Treatment delays in some cases can reduce cure fractions and increase likelihood of disease-related complications. With these cases in mind, there is a need to identify those patients who are at greatest risk of severe infection and determine what steps can we take to minimize the morbidity and mortality associated with both COVID-19 and the hematologic malignancy.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43337470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Short and Sweet: Viral 5`-UTR as a Canonical and Non-Canonical Translation Initiation Switch","authors":"Brandon M. Trainor, N. Shcherbik","doi":"10.33696/immunology.3.110","DOIUrl":"https://doi.org/10.33696/immunology.3.110","url":null,"abstract":"The replication of viruses requires host cell functions, specifically for protein synthesis, as viruses lack their own translational machinery. Failure to translate viral mRNAs and generate viral proteins would affect the propagation and evolution of a virus. Thus, independently of their size, complexity, and genomes, viruses evolved sophisticated molecular mechanisms to hijack the translational apparatus of a host in order to recruit ribosomes for efficient protein production. One of the prevalent mechanisms of translation regulation utilized by viruses is non-canonical translation initiation. It is often governed by the 5’-untranslated regions (5’-UTRs) present upstream of a protein-coding sequence in viral mRNAs, such as internal ribosome entry sites (IRESs) and capindependent translation enhancers (CITEs). Viruses can also utilize canonical translation initiation factors of a host in non-canonical ways. Understanding strategies and mechanisms used by viruses to generate proteins is an important task, as it might help develop new therapeutic interventions. We previously have demonstrated that mRNA from the genome of the black beetle virus (BBV) of the Nodaviridae family contains short and unstructured 5’-UTR, which governs translation initiation as a CITE and as a canonical translational enhancer. In this Commentary, we summarize cap-dependent and cap-independent translation initiation mechanisms and further elaborate on the unique ability of the BBV mRNA 5’-UTR to switch between these two modes of translation initiation in the context of the viral life cycle. Medical implications in treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection by targeting viral 5’-UTRs are also discussed.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"296 - 304"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43635749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler C. Hammond, Xin Xing, Lucille M. Yanckello, A. Stromberg, Ya-Hsuan Chang, P. Nelson, Ai-Ling Lin
{"title":"Human Gray and White Matter Metabolomics to Differentiate APOE and Stage Dependent Changes in Alzheimer’s Disease","authors":"Tyler C. Hammond, Xin Xing, Lucille M. Yanckello, A. Stromberg, Ya-Hsuan Chang, P. Nelson, Ai-Ling Lin","doi":"10.33696/immunology.3.123","DOIUrl":"https://doi.org/10.33696/immunology.3.123","url":null,"abstract":"Alzheimer’s disease (AD) is the most common form of dementia with hallmarks of β-amyloid (Aβ) plaques, tau tangles, and neurodegeneration. Studies have shown that neurodegeneration components, especially brain metabolic deficits, are more predictable for AD severity than Aβ and tau. However, detailed knowledge of the biochemical composition of AD brain tissue vs. normal brain tissue remains unclear. In this study, we performed a metabolomics analysis on the brain tissue of 158 community-based older adults in the University of Kentucky AD Research Center brain bank to characterize the biochemical profiles of brains with and without AD based on white/gray matter type, apolipoprotein E genotype (ε3 vs ε4 variants), and disease stage (early vs late) as all these factors influence metabolic processes. We also used machine learning to rank the top metabolites separating controls and AD in gray and white matter. Compared with control samples, we found that glutamate and creatine metabolism were more critical for predicting AD in the gray matter, while glycine, fatty acid, pyrimidine, tricarboxylic acid (TCA) cycle, and phosphatidylcholine metabolism were more critical in the white matter. In ε4 carriers, metabolites associated with the TCA cycle and oxidative phosphorylation were prominent in advanced stages compared to the early stages. In ε3 carriers, metabolites related to oxidative DNA damage, changes in inhibitory neurotransmitters, and disruptions of neuronal membranes were prominent in advanced stages compared to the early stages. In early disease, ε4 carriers had metabolites related to poor kidney function and altered neuronal sterol metabolism compared to ε3 carriers, but there were few differences between genotypes in late disease. Our results indicate that metabolism plays a pivotal role in differentiating APOE- and stage-dependent changes in AD and may facilitate precision lifestyle and dietary interventions to mitigate AD risk in the early stages, especially for ε4 carriers.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"397 - 412"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69670469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Bergen, S. Mastbergen, F. Lafeber, R. Schutgens, L. Vulpen
{"title":"Joint Health Markers in Hemophilia: The State of the Art","authors":"E. Bergen, S. Mastbergen, F. Lafeber, R. Schutgens, L. Vulpen","doi":"10.33696/immunology.3.124","DOIUrl":"https://doi.org/10.33696/immunology.3.124","url":null,"abstract":"Hemophilia is a rare congenital bleeding disorder caused by a lack of or diminished activity of clotting factor VIII (hemophilia A) or IX (hemophilia B). This deficiency leads to an increase in spontaneous and traumatic bleeding especially in the large hinged joints. Joint bleeding may result in synovial inflammation and cartilage/bone damage, ultimately leading to irreversible hemophilic arthropathy (HA) [1]. Preventing hemarthroses and accurately monitoring joint status once arthropathy has developed, is of utmost importance to prevent invalidating arthropathy and subsequent major orthopedic interventions.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41455245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glycogen Synthase Kinase-3 (GSK-3) Regulation of Inhibitory Coreceptor Expression in T-cell Immunity","authors":"Mark E Issa, C. Rudd","doi":"10.33696/immunology.3.115","DOIUrl":"https://doi.org/10.33696/immunology.3.115","url":null,"abstract":"The serine/threonine kinase, glycogen synthase kinase 3 (GSK-3) has been implicated in immune cell activation and function. Our recent studies have shown that the abrogation of GSK-3 activity down-regulates the expression of key inhibitory receptors PD-1 and LAG-3. It also regulates the expression of the transcription factor NFAT which, in turn, is responsible for inhibiting PD-1/LAG-3 transcription as well as activating the expression of cytolytic effector proteins such as perforin and granzyme B. The role of components of the Wnt signaling pathway in these events remains to be fully uncovered. This mini-review discusses the recent discoveries that have elucidated the role of the GSK-3 signaling pathway in cancer immunotherapy.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"336 - 342"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46848278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Megalin-Mediated Trafficking of Mitochondrial Intracrines: Relevance to Signaling and Metabolism","authors":"D. Sheikh-Hamad, Michael W. Holliday, Qingtian Li","doi":"10.33696/immunology.3.118","DOIUrl":"https://doi.org/10.33696/immunology.3.118","url":null,"abstract":"The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-β) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"364 - 369"},"PeriodicalIF":0.0,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47858126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}