Haley E Randolph, Katherine A Aracena, Yen-Lung Lin, Zepeng Mu, Luis B Barreiro
Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present-day susceptibility to immune-related disorders...
April 5, 2024: Immunological Reviews
Iona S Schuster, Christopher E Andoniou, Mariapia A Degli-Esposti
Natural killer (NK) cells are the prototype innate effector lymphocyte population that plays an important role in controlling viral infections and tumors. Studies demonstrating that NK cells form long-lived memory populations, akin to those generated by adaptive immune cells, prompted a revaluation of the potential functions of NK cells. Recent data demonstrating that NK cells are recruited from the circulation into tissues where they form long-lived memory-like populations further emphasize that NK cells have properties that mirror those of adaptive immune cells...
April 3, 2024: Immunological Reviews
Bikash Mishra, Lionel B Ivashkiv
Training and priming of innate immune cells involve preconditioning by PAMPs, DAMPs, and/or cytokines that elicits stronger induction of inflammatory genes upon secondary challenge. Previous models distinguish training and priming based upon whether immune activation returns to baseline prior to secondary challenge. Tolerance is a protective mechanism whereby potent stimuli induce refractoriness to secondary challenge. Training and priming are important for innate memory responses that protect against infection, efficacy of vaccines, and maintaining innate immune cells in a state of readiness; tolerance prevents toxicity from excessive immune activation...
April 3, 2024: Immunological Reviews
Mina Sadeghi, Maziar Divangahi
Conventionally, it was thought that innate immunity operated through a simple system of nonspecific responses to an insult. However, this perspective now seems overly simplistic. It has become evident that intricate cooperation and networking among various cells, receptors, signaling pathways, and protein complexes are essential for regulating and defining the overall activation status of the immune response, where the distinction between innate and adaptive immunity becomes ambiguous. Given the evolutionary timeline of vertebrates and the success of plants and invertebrates which depend solely on innate immunity, immune memory cannot be considered an innovation of only the lymphoid lineage...
April 2, 2024: Immunological Reviews
Raki Sudan, Susan Gilfillan, Marco Colonna
Group 1 innate lymphoid cells (ILCs), comprising ILC1s and natural killer cells (NK cells), belong to a large family of developmentally related innate lymphoid cells that lack rearranged antigen-specific receptors. NK cells and ILC1s both require the transcription factor T-bet for lineage commitment but additionally rely on Eomes and Hobit, respectively, for their development and effector maturation programs. Both ILC1s and NK cells are essential for rapid responses against infections and mediate cancer immunity through production of effector cytokines and cytotoxicity mediators...
April 2, 2024: Immunological Reviews
Marie Dominique Ah Kioon, Paôline Laurent, Vidyanath Chaudhary, Yong Du, Mary K Crow, Franck J Barrat
The discovery of toll-like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms of healthy immune responses as well as pathogenic mechanisms relevant to systemic autoimmune and inflammatory diseases. In systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, NA-containing immune complexes serve as TLR ligands, with distinct implications depending on the additional immune stimuli available...
March 29, 2024: Immunological Reviews
Patricia Vuscan, Brenda Kischkel, Leo A B Joosten, Mihai G Netea
Over the past decade, compelling evidence has unveiled previously overlooked adaptive characteristics of innate immune cells. Beyond their traditional role in providing short, non-specific protection against pathogens, innate immune cells can acquire antigen-agnostic memory, exhibiting increased responsiveness to secondary stimulation. This long-term de-facto innate immune memory, also termed trained immunity, is mediated through extensive metabolic rewiring and epigenetic modifications. While the upregulation of trained immunity proves advantageous in countering immune paralysis, its overactivation contributes to the pathogenesis of autoinflammatory and autoimmune disorders...
March 29, 2024: Immunological Reviews
Andrew J Konecny, Yin Huang, Manu Setty, Martin Prlic
Mucosal-associated invariant T (MAIT) cells have a semi-invariant T-cell receptor that allows recognition of antigen in the context of the MHC class I-related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1-restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon-gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL-17...
March 22, 2024: Immunological Reviews
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March 21, 2024: Immunological Reviews
Jing Zhang, Albert M Li, Emily R Kansler, Ming O Li
Cancer progression can be restrained by tumor-infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre-wired, in which innate lymphocytes and innate-like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming-dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors...
March 20, 2024: Immunological Reviews
Itziar Martinez-Gonzalez, Fumio Takei
Group 2 Innate Lymphoid Cells (ILC2s) are innate lymphocytes involved in type 2 immunity. ILC2s are abundant at the barrier tissues and upon allergen exposure, respond to epithelial-derived alarmins by producing type 2 cytokines (e.g., IL-5 and IL-13). Upon activation, some of these activated ILC2s acquire immunological memory and can mount enhanced responses upon further allergen encounters. Here, we review recent findings of the cellular and molecular mechanisms underlying immune memory in ILC2s both in mice and humans and discuss the implications of memory ILC2s in the context of allergic diseases...
March 20, 2024: Immunological Reviews
Timo Rückert, Chiara Romagnani
Clonal expansion of antigen-specific lymphocytes is the fundamental mechanism enabling potent adaptive immune responses and the generation of immune memory. Accompanied by pronounced epigenetic remodeling, the massive proliferation of individual cells generates a critical mass of effectors for the control of acute infections, as well as a pool of memory cells protecting against future pathogen encounters. Classically associated with the adaptive immune system, recent work has demonstrated that innate immune memory to human cytomegalovirus (CMV) infection is stably maintained as large clonal expansions of natural killer (NK) cells, raising questions on the mechanisms for clonal selection and expansion in the absence of re-arranged antigen receptors...
March 20, 2024: Immunological Reviews
Yoselin A Paucar Iza, Chrysothemis C Brown
Besides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long-term immunological tone of the tissue and subsequent risk of immune-mediated diseases...
March 19, 2024: Immunological Reviews
Rebekka Scholz, Desirée Brösamle, Xidi Yuan, Marc Beyer, Jonas J Neher
Microglia, the major population of brain-resident macrophages, are now recognized as a heterogeneous population comprising several cell subtypes with different (so far mostly supposed) functions in health and disease. A number of studies have performed molecular characterization of these different microglial activation states over the last years making use of "omics" technologies, that is transcriptomics, proteomics and, less frequently, epigenomics profiling. These approaches offer the possibility to identify disease mechanisms, discover novel diagnostic biomarkers, and develop new therapeutic strategies...
March 16, 2024: Immunological Reviews
Nicolas Serafini, James P Di Santo
Group 3 innate lymphoid cells (ILC3s) are tissue-resident immune lymphocytes that critically regulate intestinal homeostasis, organogenesis, and immunity. ILC3s possess the capacity to "sense" the inflammatory environment within tissues, especially in the context of pathogen challenges that imprints durable non-antigen-specific changes in ILC3 function. As such, ILC3s become a new actor in the emerging field of trained innate immunity. Here, we summarize recent discoveries regarding ILC3 responses to bacterial challenges and the role these encounters play in triggering trained innate immunity...
March 16, 2024: Immunological Reviews
Shane M O'Carroll, Fiona D R Henkel, Luke A J O'Neill
Over the past decade, there has been a surge in discoveries of how metabolic pathways regulate immune cell function in health and disease, establishing the field of immunometabolism. Specifically, pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and those involving lipid metabolism have been implicated in regulating immune cell function. Viral infections cause immunometabolic changes which lead to antiviral immunity, but little is known about how metabolic changes regulate interferon responses...
March 11, 2024: Immunological Reviews
Adnan Moinuddin, Sophie M Poznanski, Ana L Portillo, Jonathan K Monteiro, Ali A Ashkar
Natural Killer (NK) cells are a top contender in the development of adoptive cell therapies for cancer due to their diverse antitumor functions and ability to restrict their activation against nonmalignant cells. Despite their success in hematologic malignancies, NK cell-based therapies have been limited in the context of solid tumors. Tumor cells undergo various metabolic adaptations to sustain the immense energy demands that are needed to support their rapid and uncontrolled proliferation. As a result, the tumor microenvironment (TME) is depleted of nutrients needed to fuel immune cell activity and contains several immunosuppressive metabolites that hinder NK cell antitumor functions...
March 9, 2024: Immunological Reviews
Krist Antunes Fernandes, Ai Ing Lim
Maternal environmental exposures, particularly during gestation and lactation, significantly influence the immunological development and long-term immunity of offspring. Mammalian immune systems develop through crucial inputs from the environment, beginning in utero and continuing after birth. These critical developmental windows are essential for proper immune system development and, once closed, may not be reopened. This review focuses on the mechanisms by which maternal exposures, particularly to pathogens, diet, and microbiota, impact offspring immunity...
March 6, 2024: Immunological Reviews
Christa S Zerbe, Steven M Holland
Since their description by Metchnikoff in 1905, phagocytes have been increasingly recognized to be the entities that traffic to sites of infection and inflammation, engulf and kill infecting organisms, and clear out apoptotic debris all the while making antigens available and accessible to the lymphoid organs for future use. Therefore, phagocytes provide the gateway and the first check in host protection and immune response. Disorders in killing and chemotaxis lead not only to infection susceptibility, but also to autoimmunity...
March 1, 2024: Immunological Reviews
Leen Hermans, Timothy E O'Sullivan
NK cells are short-lived innate lymphocytes that can mediate antigen-independent responses to infection and cancer. However, studies from the past two decades have shown that NK cells can acquire transcriptional and epigenetic modifications during inflammation that result in increased survival and lifespan. These findings blur the lines between the innate and adaptive arms of the immune system, and suggest that the homeostatic mechanisms that govern the persistence of innate immune cells are malleable. Indeed, recent studies have shown that NK cells undergo continuous and strictly regulated adaptations controlling their survival during development, tissue residency, and following inflammation...
March 1, 2024: Immunological Reviews
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