{"title":"Preliminary Evidence of Differentially Induced Immune Responses by Microparticle-adsorbed LPS in Patients with Crohn's Disease.","authors":"P Ashwood","doi":"10.33696/immunology.4.152","DOIUrl":"10.33696/immunology.4.152","url":null,"abstract":"<p><p>Inorganic microparticles are ubiquitous in the modern Western diet present as food additives and are actively scavenged by microfold (M) cells overlying human intestinal lymphoid aggregates. In Crohn's disease (CD), inflammation is caused by the inability of the intestinal mucosa to sustain tolerance to gut luminal factors including bacteria and their by-products. Having large, highly charged surface areas dietary particles can avidly bind biomolecules such as lipopolysaccharide (LPS). The aim of this paper was to examine whether the dietary particle, titanium dioxide (TiO<sub>2</sub>), modified cellular immune responses to LPS differently in peripheral blood mononuclear cells (PBMC) from CD patients compared with healthy controls. Our data showed that LPS-associated particles predominantly stimulated release of IL-1β and induced concurrent cell death in peripheral monocytes following particle uptake in both health and disease. In addition, IL-1β release was increased more in CD patients compared with controls following particle stimulation. In conclusion, LPS adsorption to dietary particulates provides a mechanism for stimulation of phagocytic mononuclear cells and may cause aggravation of mucosal immune responses in inflammatory conditions of the bowel such as CD, irritable bowel syndrome, and autism spectrum disorder and schizophrenia associated gastrointestinal conditions, by immune priming mediated through increased production of pro-inflammatory cytokines.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 6","pages":"211-218"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9077777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III.","authors":"Saurabh Mishra, Richard J Maraia","doi":"10.33696/immunology.4.133","DOIUrl":"10.33696/immunology.4.133","url":null,"abstract":"<p><p>Nuclear RNA polymerase (Pol) III synthesizes large amounts of tRNAs and other short non-coding (nc)RNAs by a unique process that involves a termination-associated reinitiation-recycling mechanism. In addition to its two largest of 17 subunits, which contribute to active center RNA-DNA binding and catalytic site, a smaller subunit of ~110 aa (yeast C11, human RPC10) monitors this site, can modify its activity, and is essential for reinitiation-recycling. Distinct, but relevant to human immunity is cytoplasmic (cyto-)Pol III that is a direct sensor of AT-rich viral DNA from which it synthesizes 5'-ppp-RNA signaling molecules that activate interferon (IFN) production. Mutations in genes encoding Pol III subunits cause severe anti-viral immunodeficiency although the mechanisms responsible for cyto-Pol III initiation on this AT-rich DNA are unknown. Cyto-Pol III has also been implicated in inducing IFN in response to cytosolic mitochondrial DNA in autoimmune dysfunction. A focus of this commentary is recent biochemical and genetics research that examined the roles of the individual domains of C11 in the Pol III termination-associated reinitiation-recycling process as well as more recent cryo-EM structural and accompanying analyses, that are considered in evolutionary and other biological contexts. The N-terminal domain (NTD) of C11/RPC10 anchors at the periphery of Pol III from which a highly conserved linker extends to the mobile C-terminal RNA cleavage domain that can reach into the active center and rescue arrested complexes. Biochemical data indicate separable activities for the NTD and CTD in the transcription cycle, whereas the NTD-Linker can confer the evolutionary unique Pol III termination-reinitiation-recycling activity. A model produced from single particle cryo-EM conformations indicates that the C11-Linker-CTD swings in and out of the active center coordinated with allosteric movements of the DNA-binding clamp by the largest subunit, coupling termination to reinitiation-recycling. These may be relevant to DNA loading by cyto-Pol III during immune signaling.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":"65-71"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucille M Yanckello, Brian Fanelli, Scott McCulloch, Xin Xing, McKenna Sun, Tyler C Hammond, Rita Colwell, Zezong Gu, Aaron C Ericsson, Ya-Hsuan Chang, Adam D Bachstetter, Ai-Ling Lin
{"title":"Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.","authors":"Lucille M Yanckello, Brian Fanelli, Scott McCulloch, Xin Xing, McKenna Sun, Tyler C Hammond, Rita Colwell, Zezong Gu, Aaron C Ericsson, Ya-Hsuan Chang, Adam D Bachstetter, Ai-Ling Lin","doi":"10.33696/immunology.4.132","DOIUrl":"10.33696/immunology.4.132","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 2","pages":"50-64"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Return of Tocilizumab for Patients with COVID-19 Pneumonia","authors":"Kathy Tin, A. Fernandes, Roderick A. Go","doi":"10.33696/immunology.3.119","DOIUrl":"https://doi.org/10.33696/immunology.3.119","url":null,"abstract":"The COVID-19 pandemic has now impacted the global population for over a year. It has been devastating for many and has challenged us all in many ways. While the advent of vaccinations looks to curtail the number of cases, multiple challenges to ending the pandemic remain, including the advent of variants, vaccine hesitancy, access to vaccines, and the impaired efficacy of vaccines in immunocompromised persons. Thus, it is still essential to continue investigating treatments for COVID-19.","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":"45635610","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":"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}