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Science (New York, N.Y.) Mar 2021Microbial roles in cancer formation, diagnosis, prognosis, and treatment have been disputed for centuries. Recent studies have provocatively claimed that bacteria,... (Review)
Review
Microbial roles in cancer formation, diagnosis, prognosis, and treatment have been disputed for centuries. Recent studies have provocatively claimed that bacteria, viruses, and/or fungi are pervasive among cancers, key actors in cancer immunotherapy, and engineerable to treat metastases. Despite these findings, the number of microbes known to directly cause carcinogenesis remains small. Critically evaluating and building frameworks for such evidence in light of modern cancer biology is an important task. In this Review, we delineate between causal and complicit roles of microbes in cancer and trace common themes of their influence through the host's immune system, herein defined as the immuno-oncology-microbiome axis. We further review evidence for intratumoral microbes and approaches that manipulate the host's gut or tumor microbiome while projecting the next phase of experimental discovery.
Topics: Adaptive Immunity; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Bacterial Physiological Phenomena; Carcinogenesis; Gastrointestinal Microbiome; Genetic Engineering; Host Microbial Interactions; Humans; Immunomodulation; Immunotherapy; Lymphoid Tissue; Microbiota; Neoplasms; Oncolytic Virotherapy; Tumor Microenvironment; Virus Physiological Phenomena
PubMed: 33766858
DOI: 10.1126/science.abc4552 -
Frontiers in Immunology 2020The contribution of dendritic cell (DC) antigen cross-presentation to the activation of CD8 T lymphocytes for immune defense against tumors, viruses, and intracellular... (Review)
Review
The contribution of dendritic cell (DC) antigen cross-presentation to the activation of CD8 T lymphocytes for immune defense against tumors, viruses, and intracellular pathogens has been recognized widely. Although originally thought to be an exclusive characteristic of DCs, recently also other immune cells, particularly macrophages, have been shown capable of cross-presentation. Here we provide an overview of and evidence on cross-presentation by macrophages. As we discuss, it is now firmly established that various types of tissue-resident macrophages are able to cross-present via similar cellular pathways as DCs. This is based on a wide range of antigens in macrophages from many different tissue origins such as blood, tumors, and lymphoid tissue. However, the physiological relevance of macrophage cross-presentation with potential contributions to activation of CD8 T lymphocytes is still mostly unknown. While cross-presentation by various types of proinflammatory macrophages might be involved in cross-priming of naive CD8 T lymphocytes, it might also be involved in local reactivation of memory and/or effector CD8 T lymphocytes. Moreover, cross-presentation by anti-inflammatory macrophages could be related to immune tolerance. Because cross-presentation promotes the initiation and potentiation of antigen-specific CD8 T lymphocyte responses, stimulating macrophages to cross-present antigen might be a promising strategy for antitumor or antiviral therapies.
Topics: Animals; Antigen Presentation; Antigens; Biomarkers; CD8-Positive T-Lymphocytes; Cell Communication; Cross-Priming; Dendritic Cells; Humans; Lymphocyte Activation; Lymphoid Tissue; Macrophages; Organ Specificity; Signal Transduction
PubMed: 32733446
DOI: 10.3389/fimmu.2020.01276 -
Nutrients Aug 2019A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune...
A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.
Topics: Diet; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Immune System; Inflammation; Lymphoid Tissue; Nutritional Status
PubMed: 31426423
DOI: 10.3390/nu11081933 -
Cellular & Molecular Immunology Jun 2020Tertiary lymphoid structures (TLS) are ectopic lymphoid formations that form within nonlymphoid tissue. They share structural and functional characteristics with... (Review)
Review
Tertiary lymphoid structures (TLS) are ectopic lymphoid formations that form within nonlymphoid tissue. They share structural and functional characteristics with secondary lymphoid structures such as lymph nodes and can contain B-cell follicles and germinal centers surrounded by a T-cell region. TLS have been described in several types of cancers and are usually associated with positive patient outcomes. However, TLS differ vastly in cellular composition and location within tissue types. In this review, we discuss factors confounding the interpretation of the evidence for a prognostic role for TLS in cancer and frame these factors in the context of translation to regular clinical use.
Topics: Humans; Models, Biological; Neoplasms; Practice Patterns, Physicians'; Prognosis; Tertiary Lymphoid Structures; Treatment Outcome
PubMed: 32415259
DOI: 10.1038/s41423-020-0457-0 -
Nature Oct 2019Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains...
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.
Topics: Blood Cells; Cellular Microenvironment; Female; Fetus; Flow Cytometry; Gene Expression Profiling; Hematopoiesis; Humans; Liver; Lymphoid Tissue; Single-Cell Analysis; Stem Cells
PubMed: 31597962
DOI: 10.1038/s41586-019-1652-y -
Frontiers in Immunology 2022CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding... (Review)
Review
CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding to its receptor, CXCR5, CXCL13 plays an important role in lymphoid neogenesis, lymphoid organization, and immune responses. Recent studies have found that CXCL13 and its receptor CXCR5 are implicated in the pathogenesis of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, myasthenia gravis, and inflammatory bowel disease. In this review, we discuss the biological features of CXCL13 and CXCR5 and the recent findings on the pathogenic roles of the CXCL13/CXCR5 axis in autoimmune diseases. Furthermore, we discuss the potential role of CXCL13 as a disease biomarker and therapeutic target in autoimmune diseases.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Chemokine CXCL13; Dendritic Cells, Follicular; Humans; Lymphoid Tissue; Receptors, CXCR5
PubMed: 35309354
DOI: 10.3389/fimmu.2022.850998 -
BMJ Paediatrics Open Apr 2023Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the... (Review)
Review
Adenoids (nasopharyngeal tonsils), being part of Waldeyer's ring, are masses of lymphoid tissues located at the junction of the roof and the posterior wall of the nasopharynx. Adenoids play an important role in the development of the immune system and serve as a defence against infections, being the first organs that come into contact with respiratory and digestive antigens. The causes of adenoid hypertrophy are not fully known. They are most likely associated with aberrant immune reactions, infections, environmental exposures and hormonal or genetic factors. The aim of this review is to summarise the current knowledge of adenoid hypertrophy in children and associated diseases. Adenoid hypertrophy has many clinical manifestations that are frequent in the paediatric population and is accompanied by various comorbidities.
Topics: Humans; Child; Adenoids; Clinical Relevance; Nasopharynx; Lymphoid Tissue; Hypertrophy
PubMed: 37045541
DOI: 10.1136/bmjpo-2022-001710 -
Immunity Nov 2020Understanding the earliest immune responses following HIV infection is critical to inform future vaccines and therapeutics. Here, we review recent prospective human... (Review)
Review
Understanding the earliest immune responses following HIV infection is critical to inform future vaccines and therapeutics. Here, we review recent prospective human studies in at-risk populations that have provided insight into immune responses during acute infection, including additional relevant data from non-human primate (NHP) studies. We discuss the timing, nature, and function of the diverse immune responses induced, the onset of immune dysfunction, and the effects of early anti-retroviral therapy administration. Treatment at onset of viremia mitigates peripheral T and B cell dysfunction, limits seroconversion, and enhances cellular antiviral immunity despite persistence of infection in lymphoid tissues. We highlight pertinent areas for future investigation, and how application of high-throughput technologies, alongside targeted NHP studies, may elucidate immune response features to target in novel preventions and cures.
Topics: Acute Disease; Adaptive Immunity; Animals; Antiretroviral Therapy, Highly Active; Biological Evolution; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytokines; Disease Management; HIV; HIV Infections; Host-Pathogen Interactions; Humans; Immunity; Immunity, Innate; Inflammation Mediators; Lymphoid Tissue; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Time-to-Treatment; Treatment Outcome; Viral Load
PubMed: 33207216
DOI: 10.1016/j.immuni.2020.10.015 -
Nature Medicine Jan 2021Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition,...
Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
Topics: Adjuvants, Immunologic; B-Lymphocytes; COVID-19 Vaccines; Germinal Center; Hemagglutinin Glycoproteins, Influenza Virus; Humans; In Vitro Techniques; Influenza Vaccines; Lymphoid Tissue; Measles-Mumps-Rubella Vaccine; Organoids; Palatine Tonsil; Rabies Vaccines; T-Lymphocytes
PubMed: 33432170
DOI: 10.1038/s41591-020-01145-0 -
Nature Jul 2022The nervous and immune systems are intricately linked. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks...
The nervous and immune systems are intricately linked. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues through skeletal-muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signalling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin-releasing hormone neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, therefore calibrating the ability of the immune system to respond to physical threats.
Topics: Animals; Bone Marrow Cells; Brain; COVID-19; Chemokines; Disease Susceptibility; Fear; Glucocorticoids; Humans; Leukocytes; Lymphocytes; Lymphoid Tissue; Mice; Monocytes; Motor Neurons; Neural Pathways; Neutrophils; Optogenetics; Orthomyxoviridae Infections; Paraventricular Hypothalamic Nucleus; SARS-CoV-2; Stress, Psychological
PubMed: 35636458
DOI: 10.1038/s41586-022-04890-z