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1.
Braz. j. biol ; 84: e250556, 2024. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1360208

ABSTRACT

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.


Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.


Subject(s)
Animals , Mice , Exosomes , Tumor Microenvironment , Immune System , Neoplasm Metastasis , Neoplasms
2.
Orphanet J Rare Dis ; 17(1): 335, 2022 09 02.
Article in English | MEDLINE | ID: mdl-36056365

ABSTRACT

BACKGROUND: Genetic mitochondrial diseases represent a significant challenge to human health. These diseases are extraordinarily heterogeneous in clinical presentation and genetic origin, and often involve multi-system disease with severe progressive symptoms. Mitochondrial diseases represent the most common cause of inherited metabolic disorders and one of the most common causes of inherited neurologic diseases, yet no proven therapeutic strategies yet exist. The basic cell and molecular mechanisms underlying the pathogenesis of mitochondrial diseases have not been resolved, hampering efforts to develop therapeutic agents. MAIN BODY: In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease. CONCLUSIONS: Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.


Subject(s)
Leigh Disease , Mitochondrial Diseases , Nervous System Diseases , Humans , Immune System/metabolism , Leigh Disease/genetics , Leigh Disease/metabolism , Mitochondria/metabolism , Mitochondrial Diseases/genetics , Nervous System Diseases/metabolism
3.
Int J Mol Sci ; 23(17)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36076909

ABSTRACT

In humans, mitochondria play key roles in the regulation of cellular functions, such as the regulation of the innate immune response and are targets of several pathogenic viruses and bacteria. Mycobacteria are intracellular pathogens that infect cells important to the immune system of organisms and target mitochondria to meet their energy demands. In this review, we discuss the main mechanisms by which mitochondria regulate the innate immune response of humans to mycobacterial infection, especially those that cause tuberculosis and leprosy. Notably, the importance of mitochondrial haplogroups and ancestry studies for mycobacterial diseases is also discussed.


Subject(s)
Leprosy , Mycobacterium , Tuberculosis , Humans , Immune System , Leprosy/genetics , Mitochondria/genetics , Mycobacterium/genetics , Mycobacterium leprae , Tuberculosis/genetics , Tuberculosis/microbiology
4.
Development ; 149(18)2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36162816

ABSTRACT

Retrotransposon Gag-like 5 [RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)] and RTL6 (also known as SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. They, respectively, encode a strongly acidic and extremely basic protein, and are well conserved among the eutherians. Here, we report that RTL5 and RTL6 are microglial genes with roles in the front line of innate brain immune response. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and appeared as extracellular dots and granules in the central nervous system. These proteins display a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA, acting both cooperatively and/or independently. Experiments using Rtl6 or Rtl5 knockout mice provided additional evidence that RTL6 and RTL5 act as factors against LPS and dsRNA, respectively, in the brain, providing the first demonstration that retrovirus-derived genes play a role in the eutherian innate immune system. Finally, we propose a model emphasizing the importance of extra-embryonic tissues as the origin site of retrovirus-derived genes. This article has an associated 'The people behind the papers' interview.


Subject(s)
Lipopolysaccharides , Retroviridae , Animals , Brain/metabolism , Eutheria/genetics , Humans , Immune System , Immunity, Innate/genetics , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Mice , Mice, Knockout , Microglia/metabolism , RNA, Double-Stranded/metabolism , Retroelements/genetics , Retroviridae/genetics
5.
Clin Lymphoma Myeloma Leuk ; 22 Suppl 2: S377, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36164088

ABSTRACT

CONTEXT: Diffuse large B-cell lymphoma (DLBCL) represents the most common lymphoma in adults with heterogeneous clinical features and aggressive behavior. Despite that, its etiology remains unknown. Recently, the deregulation of Notch signaling has been found to be crucial for cancer biology through tumor-promoting or suppressing mechanisms. OBJECTIVE: To evaluate the RNA expression level of Notch receptors (NOTCH1-4), canonical Notch ligands either Delta-like (DLL1, DLL3, DLL4) or Serrate-like (JAG1, JAG2), as well as the Notch downstream genes (HES1, HEY1) in DLBCL utilizing online tools and publicly available databases. METHODS: Data from DLBCL patients and matched healthy controls were retrieved from the TCGA- DLBC and GTEx. The expression of the Notch pathway-related genes in DLBCL and controls were compared. The association of the Notch members with immune cell infiltration and other common cancer-related pathways was assessed using the TIMER2 database and GSCALite server, respectively. RESULTS: A total of 337 normal blood samples were extracted from GTEx and 48 samples were extracted from TCGA-DLBC (46% were males and 54% were females with a median age of 57.5 years). The clinical stage was available for 42 patients only; 19% in stage I, 40.5% in stage II, 11.9% patients in stage III, and 28.6% patients in stage IV. The expression levels of NOTCH3/4, DLL1/3/4, JAG1/2, and HEY1 were significantly upregulated in the DLBCL samples compared to the controls. Moreover, high expression levels of DLL1 were associated with the advanced clinical stage (stage IV). The correlation between the upregulated Notch receptors and ligands and the infiltration level of immune cells revealed that the NOTCH3, DLL1/4 and JAG1 have a positive correlation with neutrophils and a negative correlation with a regulatory T-cell. The pathways analysis indicated that NOTCH3/4, DLL1/4, and JAG1 predominantly activate the EMT pathway. Furthermore, NOTCH4, DLL1, JAG1, and HES1 predominantly inhibit the cell cycle and apoptosis pathways. CONCLUSIONS: These data showed that DLL1 might play a pivotal role in the prognosis of DLBCL through immune system modulation and interaction with cancer-related pathways. This suggests that DLL1 could be a novel prognostic biomarker, risk stratification factor, and attractive therapeutic target for DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Receptors, Notch , Adult , Biomarkers , Female , Humans , Immune System/metabolism , Intracellular Signaling Peptides and Proteins , Ligands , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle Aged , RNA , Receptors, Notch/genetics , Receptors, Notch/metabolism
6.
Gastroenterol Clin North Am ; 51(3): 667-680, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36153116

ABSTRACT

The human microbiome has been recognized as increasingly important to health and disease. This is especially prescient in the development of various cancers, their progression, and the microbiome's modulation of various anticancer therapeutics. Mechanisms behind these interactions have been increasingly well described through modulation of the host immune system as well as induction of genetic changes and local inactivation of cancer therapeutics. Here, we review these associations for a variety of gastrointestinal malignancies as well as contemporary strategies proposed to leverage these associations to improve cancer treatment outcomes.


Subject(s)
Gastrointestinal Neoplasms , Microbiota , Humans , Immune System
7.
PLoS One ; 17(9): e0274228, 2022.
Article in English | MEDLINE | ID: mdl-36094909

ABSTRACT

Serum or plasma have been the primary focus of proteomics studies for COVID-19 to identity biomarkers and potential drug targets. The nasal mucosal environment which consists of lipids, mucosal immune cells, and nasal proteome, has been largely neglected but later revealed to have critical role combating SARS-CoV-2 infection. We present a bottom-up proteomics investigation of the host response to SARS-CoV-2 infection in the nasopharyngeal environment, featuring a noninvasive approach using proteins in nasopharyngeal swabs collected from groups of 76 SARS-CoV-2 positive and 76 negative patients. Results showed that 31 significantly down-regulated and 6 up-regulated proteins were identified (p < 0.05, log2 FC > 1.3) in SARS-CoV-2 positive patient samples as compared to the negatives; these proteins carry potential value as markers for the early detection of COVID-19, disease monitoring, as well as be drug targets. The down-regulation of coagulation factor 5 indicates a thrombotic abnormality in COVID-19 patients and the decreased IgG4 suggests an abnormal immune response at the point of entry in human nasopharyngeal environment, which is in consistent with KEGG and GO pathway analysis. Our study also demonstrated that mass spectrometry proteomics analysis of nasopharyngeal swabs can be used as a powerful early approach to evaluate host response to SARS-CoV-2 viral infection.


Subject(s)
COVID-19 , Complement System Proteins , Humans , Immune System , Nasopharynx , Proteomics , SARS-CoV-2
8.
Front Immunol ; 13: 935321, 2022.
Article in English | MEDLINE | ID: mdl-36119097

ABSTRACT

In this article, we will share lessons that patients with gain-of-function defects in Toll-like receptor 8 (TLR8-GOF) can teach us about the interface between bone marrow failure (BMF) disorders and inborn errors of immunity (IEI), subsequently referred to as "Interface Disorders". TLR8-GOF is a relatively young entity (from a discovery standpoint) that-through both similar and dissimilar disease characteristics-can increase our understanding of interface disorders, for example, as it pertains to pathophysiology, the genetic mechanism of disease, and related diagnostics and therapeutics. From a genetics point of view, TLR8-GOF joins a growing list of (interface) disorders that can cause disease both with germline and somatic (mosaic) genetic variants. This not only has repercussions for the diagnostic workup of these disorders, inasmuch that routine genetic testing may miss somatic variants, but has therapeutic implications as well, for example, with the approach to curative treatment, such as hematopoietic stem cell transplantation. Following an introduction and schematic rendering of the interface, we will review the salient features of TLR8-GOF, with the understanding that the phenotype of this new disorder is likely not written in stone yet. In keeping with the principle of "Form Follows Function", we will discuss specific immunological biomarkers that can be measured in clinical laboratories and highlight key disease features that pertain to TLR8-GOF, and can be found in several interface disorders. As can be seen from a schematic representation, the interface provides not only opportunities for learning and collaboration with respect to shared diagnostics but also the potential for drug repurposing and precision therapeutics. Ideally, collaboration also focuses on education and teaching, such that cross-fertilization and collaboration across these disciplines can create a framework for complementary research.


Subject(s)
Immunologic Deficiency Syndromes , Toll-Like Receptor 8 , Bone Marrow Failure Disorders , Gain of Function Mutation , Humans , Immune System , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/therapy
9.
Int J Mol Sci ; 23(18)2022 Sep 18.
Article in English | MEDLINE | ID: mdl-36142818

ABSTRACT

Cancer immunotherapy has fundamentally altered cancer treatment; however, its efficacy is limited to a subset of patients in most clinical settings. The immune system plays a key role in cancer progression from tumor initiation to the metastatic state. Throughout the treatment course, communications between the immune cells in the tumor microenvironment and the immune macroenvironment, as well as interactions between the immune system and cancer cells, are dynamic and constantly evolving. To improve the clinical benefit for patients who do not respond completely to immunotherapy, the molecular mechanisms of resistance to immunotherapy must be elucidated in order to develop effective strategies to overcome resistance. In an attempt to improve and update the current understanding of the molecular mechanisms that hinder immunotherapy, we discuss the molecular mechanisms of cancer resistance to immunotherapy and the available treatment strategies.


Subject(s)
Immunotherapy , Neoplasms , Humans , Immune System/pathology , Neoplasms/pathology , Tumor Microenvironment
10.
Front Cell Infect Microbiol ; 12: 980868, 2022.
Article in English | MEDLINE | ID: mdl-36159650

ABSTRACT

Immunomodulators such as tumour necrosis factor (TNF) inhibitors are used to treat autoimmune conditions by reducing the magnitude of the innate immune response. Dampened innate responses pose an increased risk of new infections by opportunistic pathogens and reactivation of pre-existing latent infections. The alteration in immune response predisposes to increased severity of infections. TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, transplant recipients, and inflammatory bowel disease. The efficacies of immunomodulators are shown to be varied, even among those that target the same pathways. Monoclonal antibody-based TNF inhibitors have been shown to induce stronger immunosuppression when compared to their receptor-based counterparts. The variability in activity also translates to differences in risk for infection, moreover, parallel, or sequential use of immunosuppressive drugs and corticosteroids makes it difficult to accurately attribute the risk of infection to a single immunomodulatory drug. Among recipients of TNF inhibitors, Mycobacterium tuberculosis has been shown to be responsible for 12.5-59% of all infections; Pneumocystis jirovecii has been responsible for 20% of all non-viral infections; and Legionella pneumophila infections occur at 13-21 times the rate of the general population. This review will outline the mechanism of immune modulation caused by TNF inhibitors and how they predispose to infection with a focus on Mycobacterium tuberculosis, Legionella pneumophila, and Pneumocystis jirovecii. This review will then explore and evaluate how other immunomodulators and host-directed treatments influence these infections and the severity of the resulting infection to mitigate or treat TNF inhibitor-associated infections alongside antibiotics.


Subject(s)
Autoimmune Diseases , Mycobacterium tuberculosis , Pneumonia , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Humans , Immune System , Immunologic Factors/adverse effects , Immunomodulating Agents , Immunosuppression Therapy/adverse effects , Pneumonia/drug therapy , Prospective Studies , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha
11.
Front Immunol ; 13: 982026, 2022.
Article in English | MEDLINE | ID: mdl-36159789

ABSTRACT

With the goal of harnessing the host's immune system to provide long-lasting remission and cures for various cancers, the advent of immunotherapy revolutionized the cancer therapy field. Among the current immunotherapeutic strategies, immune checkpoint blockades have greatly improved the overall survival rates in certain patient populations. Of note, CTLA4 and PD-1/PD-L1 are two major non-redundant immune checkpoints implicated in promoting cancer immune evasion, and ultimately lead to relapse. Antibodies or inhibitors targeting these two c+heckpoints have achieved some encouraging clinical outcomes. Further, beyond the canonical immune checkpoints, more inhibitory checkpoints have been identified. Herein, we will summarize recent progress in immune checkpoint blockade therapies, with a specific focus on key pre-clinical and clinical results of new immune checkpoint therapies for cancer. Given the crucial roles of immune checkpoint blockade in oncotherapy, drugs targeting checkpoint molecules expressed by both cancer and immune cells are in clinical trials, which will be comprehensively summarized in this review. Taken together, investigating combinatorial therapies targeting immune checkpoints expressed by cancer cells and immune cells will greatly improve immunotherapies that enhance host elimination of tumors.


Subject(s)
B7-H1 Antigen , Neoplasms , CTLA-4 Antigen , Humans , Immune Checkpoint Inhibitors , Immune System , Programmed Cell Death 1 Receptor
12.
Front Immunol ; 13: 949928, 2022.
Article in English | MEDLINE | ID: mdl-36059504

ABSTRACT

The immune response is remodeled with aging in a process called immunosenescence. Some immunologists conceive immunosenescence as an adaptation of immunity to the aged immune-environment rather than a merely collapsed reactivity of immune cells against microbes and tumor cells. Others believe on an uninterrupted activation of the innate immune system with aging, leading to a low grade, sterile and chronic proinflammatory state called inflammaging. For instance, it is possible that chronic infection by cytomegalovirus leads to persistent production of viral load. This phenomenon offers periodic stimuli to the immune system that ultimately contribute to the remodeling of the immune response. If investigating immunosenescence at the cellular level is already a difficult task, considering the population level is much more complex. However, by studying immunosenescence at the population level, we can extract valuable results with viable applications. While studies with animal models allow scientists to deepen their understanding of the mechanisms of immunosenescence, studying large populations can bring practical innovations to medicine and the health system. Many researchers and funders have dedicated themselves to producing methods for the evaluation of immunosenescence on a large scale, aiming to elucidate new mechanisms by which diseases are established in the elderly. The description of how the immune response is remodeled with aging emerges as a new tool to identify the subset of subjects in which unhealthy aging is a matter of time, to help better individualize clinical management and select patients who may benefit. of early interventions. This review focuses on functional assays as valuable methods for measuring the remodeling of the immune response with aging and discuss their clinical impact. We also recall fundamental concepts for understanding the aging process of the immune response. In addition, we highlight future prospects for immunosenescence research.


Subject(s)
Immunosenescence , Aging , Animals , Humans , Immune System , Inflammation
13.
Front Immunol ; 13: 979469, 2022.
Article in English | MEDLINE | ID: mdl-36072591

ABSTRACT

Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body's intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.


Subject(s)
Nanostructures , Neoplasms , Biocompatible Materials , Humans , Immune System/pathology , Immunotherapy
14.
Front Immunol ; 13: 990874, 2022.
Article in English | MEDLINE | ID: mdl-36081513

ABSTRACT

Akt is a PI3K-activated serine-threonine kinase that exists in three distinct isoforms. Akt's expression in most immune cells, either at baseline or upon activation, reflects its importance in the immune system. While Akt is most highly expressed in innate immune cells, it plays crucial roles in both innate and adaptive immune cell development and/or effector functions. In this review, we explore what's known about the role of Akt in innate and adaptive immune cells. Wherever possible, we discuss the overlapping and distinct role of the three Akt isoforms, namely Akt1, Akt2, and Akt3, in immune cells.


Subject(s)
Immune System , Proto-Oncogene Proteins c-akt , Cell Differentiation , Immune System/metabolism , Protein Isoforms/metabolism , Proto-Oncogene Proteins c-akt/metabolism
15.
Front Immunol ; 13: 977175, 2022.
Article in English | MEDLINE | ID: mdl-36090980

ABSTRACT

The increasing resistance to antibiotic treatments highlights the need for the development of new antimicrobial agents. Antimicrobial peptides (AMPs) have been studied to be used in clinical settings for the treatment of infections. Endogenous AMPs represent the first line defense of the innate immune system against pathogens; they also positively interfere with infection-associated inflammation. Interestingly, AMPs influence numerous biological processes, such as the regulation of the microbiota, wound healing, the induction of adaptive immunity, the regulation of inflammation, and finally express anti-cancer and cytotoxic properties. Numerous peptides identified in chromaffin secretory granules from the adrenal medulla possess antimicrobial activity: they are released by chromaffin cells during stress situations by exocytosis via the activation of the hypothalamo-pituitary axis. The objective of the present review is to develop complete informations including (i) the biological characteristics of the AMPs produced after the natural processing of chromogranins A and B, proenkephalin-A and free ubiquitin, (ii) the design of innovative materials and (iii) the involvement of these AMPs in human diseases. Some peptides are elective biomarkers for critical care medicine, may play an important role in the protection of infections (alone, or in combination with others or antibiotics), in the prevention of nosocomial infections, in the regulation of intestinal mucosal dynamics and of inflammation. They could play an important role for medical implant functionalization, such as catheters, tracheal tubes or oral surgical devices, in order to prevent infections after implantation and to promote the healing of tissues.


Subject(s)
Adrenal Medulla , Chromaffin Cells , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides , Antimicrobial Peptides , Humans , Immune System , Inflammation/drug therapy
16.
Front Immunol ; 13: 904342, 2022.
Article in English | MEDLINE | ID: mdl-36110838

ABSTRACT

The clinical handling of chronic virus infections remains a challenge. Here we describe recent progress in the understanding of virus - host interaction dynamics. Based on the systems biology concept of multi-stability and the prediction of multiplicative cooperativity between virus-specific cytotoxic T cells and neutralising antibodies, we argue for the requirements to engage multiple immune system components for functional cure strategies. Our arguments are derived from LCMV model system studies and are translated to HIV-1 infection.


Subject(s)
HIV Infections , Virus Diseases , Antibodies, Neutralizing/therapeutic use , Humans , Immune System
17.
Front Cell Infect Microbiol ; 12: 953718, 2022.
Article in English | MEDLINE | ID: mdl-36046747

ABSTRACT

The human gut microbiota are critical for preserving the health status because they are required for digestion and nutrient acquisition, the development of the immune system, and energy metabolism. The gut microbial composition is greatly influenced by the colonization of the recalcitrant pathogen Helicobacter pylori (H. pylori) and the conventional antibiotic regimens that follow. H. pylori is considered to be the main microorganism in gastric carcinogenesis, and it appears to be required for the early stages of the process. However, a non-H. pylori microbiota profile is also suggested, primarily in the later stages of tumorigenesis. On the other hand, specific groups of gut microbes may produce beneficial byproducts such as short-chain fatty acids (acetate, butyrate, and propionate) that can modulate inflammation and tumorigenesis pathways. In this review, we aim to present how H. pylori influences the population of the gut microbiota to modify the host immunity and trigger the development of gastric carcinogenesis. We will also highlight the effect of the gut microbiota on immunotherapeutic approaches such as immune checkpoint blockade in cancer treatment to present a perspective for further development of innovative therapeutic paradigms to prevent the progression of H. pylori-induced stomach cancer.


Subject(s)
Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Carcinogenesis , Helicobacter Infections/complications , Helicobacter Infections/drug therapy , Homeostasis , Humans , Immune System
19.
Trends Neurosci ; 45(10): 733-748, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36075783

ABSTRACT

Neurodegenerative diseases are a major cause of death and disability worldwide and are influenced by many factors including age, genetics, and injuries. While these diseases are often thought to result from the accumulation and spread of aberrant proteins, recent studies have demonstrated that they can be shaped by the innate and adaptive immune system. Resident myeloid cells typically mount a sustained response to the degenerating CNS, but peripheral leukocytes such as T and B cells can also alter disease trajectories. Here, we review the sometimes-dichotomous roles played by immune cells during neurodegenerative diseases and explore how brain trauma can serve as a disease initiator or accelerant. We also offer insights into how failure to properly resolve a CNS injury might promote the development of a neurodegenerative disease.


Subject(s)
Neurodegenerative Diseases , Humans , Immune System , Immunity, Innate/physiology , Neurodegenerative Diseases/metabolism
20.
Pestic Biochem Physiol ; 187: 105212, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36127056

ABSTRACT

Lymantria dispar is one of the most devastating forest pests worldwide. Fungal biopesticides have great potential as alternatives owing to their high lethality to pests and eco-friendly feature, which is, however, often severely compromised by the pests' innate immunity. A better understanding of the antifungal immune system in L. dispar would significantly facilitate the development of the biopesticide. Here, we investigated phylogenetic characteristics of immunity-related genes as well as the tissue expression patterns in L. dispar after the infection of an entomopathogen Beauveria bassiana using RNA-sequencing data. Results showed most immune genes remain at a low level of response after 24 h post-infection (HPI). Almost all genes in the Toll pathway were significantly up-regulated at 48 HPI, and SPH1, SPN6, Toll6, Toll12, Myd88, pelle, and Drosal were significantly down-regulated at 72 HPI. Immunoblotting analysis revealed that the protein levels of ßGRP3 and PPO1 were significantly upregulated at 24 and 48 HPI, while Myd88 was downregulated at 24 HPI, which was further confirmed by Quantitative real-time PCR experiments. Moreover, the relative content of H2O2, a potent reactive oxygen species (ROS), was significantly increased with the decrease of the total antioxidant capacity, indicating that oxidative stress system positively participates in the clearance of the pathogenic fungus. Together, our study provides detailed genetic characteristics of antifungal immunity as well as profiling of the host defense against entomopathogenic infection, and comprehensive insight into molecular interaction between L. dispar and the entomopathogen.


Subject(s)
Beauveria , Antifungal Agents , Antioxidants , Beauveria/physiology , Biological Control Agents , Hydrogen Peroxide , Immune System , Myeloid Differentiation Factor 88 , Phylogeny , RNA , Reactive Oxygen Species
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