International Reviews of Immunology最新文献

The innate lymphoid cell (ILC) system comprising of the circulating and tissue-resident cells is known to clear infectious pathogens, establish immune homeostasis as well as confer antitumor immunity. Human natural killer cells (hNKs) and other ILCs carry out mopping of the infectious pathogens and perform cytolytic activity regulated by the non-adaptive immune system. The NK cells generate immunological memory and rapid recall response tightly regulated by the adaptive immunity. The interaction of NK and B cell, and its role to induce the pathogen specific immunity is not fully understood. Hence, present article sheds light on the interaction between NK and B cells and resulting immune responses in the infectious diseases. The immune responses elicited by the NK-B cell interaction is of particular importance for developing therapeutic vaccines against the infectious pathogens. Further, experimental evidences suggest the immune-response driven by NK cell population elicits the host-specific antibodies and memory B cells. Also, recently developed humanized immune system (HIS) mice and their importance in to understanding the NK-B cell interaction and resulting pathogen specific immunity has been discussed.

Ferroptosis is a type of non-apoptotic cell death, which demonstrates a definite iron-dependent expression pattern and is associated with lipid peroxidation. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis. Ferroptosis is involved in the development and progression of various diseases, such as cancer, tissue ischemia-reperfusion injury, neurological diseases, and respiratory diseases. It has been established previously that ferroptotic cells trigger the innate immune system by releasing inflammation-linked damage-related molecules, and immune cells stimulate the inflammatory response by recognizing the operational mechanism of ferroptosis. Some anti-inflammatory drugs have been shown to inhibit ferroptosis in certain cell models. Conversely, some ferroptosis inhibitors also exert anti-inflammatory effects in certain diseases. The present review evaluated the relationship between ferroptosis and inflammation, as well as the underlying internal mechanism, and provided valuable insights into developing novel treatment strategies for inflammatory diseases and cancer.

Leishmaniasis is an exemplary paradigm of immune evasion, fraught with the perils of limited clinical assistance, escalating costs of treatment and made worse with the lack of suitable vaccine. While drugs remain central to large-scale disease control, the growing emergence of parasite resistance necessitates the need for combination therapy involving host-directed immunological agents. Also, since prolonged disease progression is associated with strong immune suppression of the host, augmentation of host immunity via restoration of the immunoregulatory circuit involving antigen-presenting cells and T-cells, activation of macrophage function and/or CD4⁺ T helper 1 cell differentiation may serve as an ideal approach to resolve severe cases of leishmaniasis. As such, therapies that embody a synergistic approach that involve direct killing of the parasite in addition to elevating host immunity are likely to pave the way for widespread elimination of leishmaniasis in the future. With this review, we aim to recapitulate the various immunotherapeutic agents found to hold promise in antileishmanial treatment both in vitro and in vivo. These include parasite-specific antigens, dendritic cell-targeted therapy, recombinant inhibitors of various components intrinsic to immune cell signaling and agonists or antagonists to immune cells and cytokines. We also summarize their abilities to direct therapeutic skewing of the host cell-immune response and review their potential to combat the disease either alone, or as adjunct modalities.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite strict control measures implemented worldwide and immunization using novel vaccines, the pandemic continues to rage due to emergence of several variants of SARS-CoV-2 with increased transmission and immune escape. The rapid spread of variants of concern (VOC) in the recent past has created a massive challenge for the control of COVID-19 pandemic via the currently used vaccines. Vaccines that are safe and effective against the current and future variants of SARS-CoV-2 are essential in controlling the COVID-19 pandemic. Rapid production and massive rollout of next-generation vaccines against the variants are key steps to control the COVID-19 pandemic and to help us return to normality. Coordinated surveillance of SARS-CoV-2, rapid redesign of new vaccines and extensive vaccination are needed to counter the current SARS-CoV-2 variants and prevent the emergence of new variants. In this article, we review the latest information on the VOCs and variants of interest (VOIs) and present the information on the clinical trials that are underway on evaluating the effectiveness of COVID-19 vaccines on VOCs. We also discuss the current challenges posed by the VOCs in controlling the COVID-19 pandemic and future strategies to overcome the threat posed by the highly virulent and rapidly transmissible variants of SARS-CoV2.

Circadian locomotor output cycles kaput (Clock) and brain and muscle ARNT-like 1 (Bmal1) are two core circadian clock genes. They form a heterodimer that can bind to the E-box element in the promoters of Period circadian protein (Per) and Cryptochrome (Cry) genes, thereby inducing the rhythmic expression of circadian clock control genes. Toll-like receptors (TLRs) are type I transmembrane proteins belonging to the pattern recognition receptor (PRR) family. They can recognize a variety of pathogens and play an important role in innate immunity and adaptive immune responses. Recent studies have found that the circadian clock is closely associated with the immune system. TLRs have a certain correlation with the circadian rhythms; Bmal1 seems to be the central mediator connecting the circadian clock and the immune system. Research on Bmal1 and TLRs has made some progress, but the specific relationship between TLRs and Bmal1 remains unclear. Understanding the relationship between TLRs and Clock/Bmal1 genes is increasingly important for basic research and clinical treatment.

Neurodegenerative diseases gradually receive attention with a rapidly aging global population. The hallmark of them is a progressive neuronal loss in the brain or peripheral nervous system due to complex reasons ranging from protein aggregation, immune dysregulation to abnormal cell death. The death style of nerve cell is no longer restricted to apoptosis, autophagy and necrosis as confirmed before. With the successive discoveries of the gasdermin (GSDM) protein family and key caspase molecules in the past several decades, pyroptosis emerges as a novel kind of programmed cell death. A substantial body of evidence has recognized the close connection between pyroptosis and the occurrence and development of neurodegenerative diseases. In this review, we summarize molecular mechanisms of pyroptosis, evidences for pyroptosis involvement in neurodegenerative diseases and finally we hope to provide a novel angle for clinical decision-making.

Background: This cross-sectional and longitudinal analysis aimed to demonstrate the disparities in positive results and dissemination patterns of randomized controlled trials (RCTs) in global immuno-oncology (IO).

Methods: Phase II-IV RCTs with results reported by article publications registered on ClinicalTrials.gov in 2007-2018 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer, cancer vaccines, and immune modulators were included.

Results: Twenty-eight percent of trials were positive (72 of 258), most of which were pharma-sponsored and focused on ICI and multiple IO therapies in lung cancer, melanoma, and multiple cancer types. The recent period of trial start year, upfront registration, large sample size, high strictness score on corticosteroid/infection-related criteria, and survival endpoints were associated with positive results. Trials from Mainland China had a faster publication timeline of positive results but lacked study diversity or full reporting of negative results compared with US and multinational trials. Compared with phase II trials, phase III-IV trials had a higher average proportion of positive results (28.9% vs. 22.2%) and a more stable change over the past decade (23.65% vs. 49.24%). Positive trials yielded more secondary manuscripts (10 vs. 4), a shorter publication process of approximately two years (P < 0.001), and a superiority in the dissemination of journals with an h-index >90 (P < 0.001) compared with negative trials.

Conclusion: Disparities in positive result dissemination are widespread in IO RCTs and affected by trial features. We proposed improvements in upfront registration, procedural integrity, and adequate inclusion of rival trials reporting negative results within the earlier two years in future reviews.

B cells play a crucial role in antigen presentation, antibody production and pro-/anti-inflammatory cytokine secretion in adaptive immunity. Several translational factors including transcription factors and cytokines participate in the regulation of B cell development, with the cooperation of epigenetic regulations. Autoimmune diseases are generally characterized with autoreactive B cells and high-level pathogenic autoantibodies. The success of B cell depletion therapy in mouse model and clinical trials has proven the role of B cells in pathogenesis of autoimmune diseases. The failure of B cell tolerance in immune checkpoints results in accumulated autoreactive naïve B (B_N) cells with aberrant B cell receptor signaling and dysregulated B cell response, contributing to self-antibody-mediated autoimmune reaction. Dysregulation of translational factors and epigenetic alterations in B cells has been demonstrated to correlate with aberrant B cell compartment in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis, diabetes mellitus and pemphigus. This review is intended to summarize the interaction of translational factors and epigenetic regulations that are involved with development and differentiation of B cells, and the mechanism of dysregulation in the pathogenesis of autoimmune diseases.

Siglec-1, also known as Sialoadhesin (Sn) and CD169 is highly conserved among vertebrates and with 17 immunoglobulin-like domains is Siglec-1 the largest member of the Siglec family. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocyte. The structure of Siglec-1 is unique among siglecs and its function as a receptor is also different compared to other receptors in this class as it contains the most extracellular domains out of all the siglecs. However, the ability of Siglec-1 to internalize antigens and to pass them on to lymphocytes by allowing dendritic cells and macrophages to act as antigen presenting cells, is the main reason that has granted Siglec-1's key role in multiple human disease states including atherosclerosis, coronary artery disease, autoimmune diseases, cell-cell signaling, immunology, and more importantly bacterial and viral infections. Enveloped viruses for example have been shown to manipulate Siglec-1 to increase their virulence by binding to sialic acids present on the virus glycoproteins allowing them to spread or evade immune response. Siglec-1 mediates dissemination of HIV-1 in activated tissues enhancing viral spread via infection of DC/T-cell synapses. Overall, the ability of Siglec-1 to bind a variety of target cells within the immune system such as erythrocytes, B-cells, CD8+ granulocytes and NK cells, highlights that Siglec-1 is a unique player in these essential processes.

Introduction: Despite new approaches in the diagnosis and treatment of tuberculosis (TB), it continues to be a major health burden. Several immunotherapies that potentiate the immune response have come up as adjuncts to drug therapies against drug resistant TB strains; however, there needs to be an urgent appraisal of host specific drug targets for improving their clinical management and to curtail disease progression. Presently, various host directed therapies (HDTs) exist (repurposed drugs, nutraceuticals, monoclonal antibodies and immunomodulatory agents), but these mostly address molecules that combat disease progression.

Areas covered: The current review discusses major Mycobacterium tuberculosis (M. tuberculosis) survival paradigms inside the host and presents a plethora of host targets subverted by M. tuberculosis which can be further explored for future HDTs. The host factors unique to M. tuberculosis infection (in humans) have also been identified through an in-silico interaction mapping.

Expert opinion: HDTs could become the next-generation adjunct therapies in order to counter antimicrobial resistance and virulence, as well as to reduce the duration of existing TB treatments. However, current scientific efforts are largely directed toward combatants rather than host molecules co-opted by M. tuberculosis for its survival. This might drive the immune system to a hyper-inflammatory condition; therefore, we emphasize that host factors subverted by M. tuberculosis, and their subsequent neutralization, must be considered for development of better HDTs.