Trends in Immunology最新文献

Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell-microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.

Traumatic brain injury (TBI) is a leading cause of neurological disability, associated with higher rates of cognitive complications that negatively affect recovery. Myriad cytokine and chemokine pathways propagate the secondary responses to injury. This review discusses the integration of peripheral and central immune cytokine and chemokine signaling cascades after TBI and recovery, with a focus on preclinical work. We first discuss key cytokine and chemokine interactions influencing recovery and long-term deficits. Next, we discuss the major cell types that propagate and respond to the inflammatory process after TBI. Understanding neuroimmune signaling, utilizing recent advances in transcriptomics and immune profiling, with a focus on cytokines and chemokine after TBI reveals therapeutic targets and informs strategies to improve long-term recovery and outcomes.

The evolution of the fetal immune system within the womb is a delicate balancing act: it is trained to not reject maternal antigens, while equipping itself with 'learned' immunity to survive and thrive in the outside world. In this opinion article, we propose that a deliberate maternal touch via immune and nutritional influences, orchestrated, in part, by microbiota-derived components, imprints the fetal immune system with the needed immune memory and epigenetic marks to navigate a far less nurturing outside world, including early microbial colonizers in the newborn's intestine, pathogens and irritants, and allergens in food. We redefine the hygiene hypothesis to include prenatal maternal microbial exposures, priming fetal immune development for long-term fitness and reduced inflammatory/autoimmune disease risk.

Salmonella enterica serovar Typhimurium (STm) represents a major global health burden. Strains endemic in sub-Saharan Africa cause life-threatening invasive non-typhoidal salmonellosis (iNTS) in vulnerable populations. Studies in the iNTS-like mouse model show that STm induces profound germinal centre (GC) disruption, impairing high-affinity, long-lived antibody and memory B cell formation - affecting nascent and pre-existing GC reactions. Lipopolysaccharide (LPS) and specific STm type 3 secretion effectors drive GC collapse, but the determining bacteria-host interactions are still unclear. Although STm induces an extrafollicular (EF) B cell response generating protective antibodies, their longevity remains unclear. With no licensed human vaccine for iNTS, we propose that vaccine strategies should consider ways to protect GC integrity and include GC parameters as endpoints in preclinical trials.

Neutrophil extracellular trap (NET) formation, or NETosis, is a key innate immune response that contributes to cardiovascular diseases, including vascular inflammation, atherosclerosis, and thrombosis. In the cardiovascular system, neutrophils encounter mechanical cues such as shear stress, matrix stiffness, and cyclic stretch that influence their activation and NET release. This review examines emerging evidence linking altered mechanotransduction to dysregulated NETosis in vascular aging and cardiovascular pathology. We also highlight intracellular signalling pathways by which neutrophils sense and respond to mechanical stress. Understanding how biomechanical cues regulate NETosis may uncover novel therapeutic opportunities to control inflammation in cardiovascular disease without compromising host defence.

T cells can exchange parts of their plasma membrane along with membrane-associated proteins through trogocytosis. During trogocytosis only certain subsets of membrane-associated proteins seem to be exchanged suggesting a fine-tuned mechanism regulating the selection of what can be transferred. In this review, we describe potential models of trogocytosis and discuss mechanisms that could regulate this process in T cells. Additionally, we delve into how exchanged proteins polarize on the surface of recipient cells, discuss how trogocytosis allows T cells to acquire new functions, and summarize ways to modulate this process in T cells. Understanding trogocytosis can help us better understand the immune response and develop more effective immunotherapies.

Interactions between autoimmune disorders and lymphoid malignancies have long been recognized; for instance, with prominent autoimmune manifestations in B- and T-cell lymphomas and an increased risk of lymphoma development in individuals with autoimmune diseases. More recently, several lines of evidence have shown that these two disease types have shared origins, defined by common genetic lesions and pathogenic cell states. Recent work suggests that the safeguards that protect normal lymphocyte development and adaptive immunity against the development of autoimmune diseases and lymphoid malignancies are based on similar sensing mechanisms of pathological lymphocytes. Here, we propose that mechanisms of negative selection that are designed to eliminate autoreactive lymphocytes also operate in suppressing the development of lymphoid malignancies.

Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), but their heterogeneity, driven by tumor-derived cues, poses challenges for therapeutic targeting and underscores the need for precise macrophage reprogramming strategies. Through a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen, Marelli et al. identified chemosensors as lipid-sensing regulators of macrophage activity, revealing new therapeutic avenues.

Humanized mouse models with transgenic expression of human myelopoiesis-supporting growth factors have enhanced human myeloid cell engraftment and improved the study of human innate immune responses. Here, we discuss the remaining challenges associated with studying innate immunity in humanized NSG-SGM3 and MISTRG mice, as well as potential advances to overcome them.

An allelic variant of the autophagy gene ATG16L1 (T300A) is a genetic risk factor for Crohn's disease. However, over 50% of the global population carries at least one copy. Yao et al. have demonstrated a heterozygote advantage, where the pathogen-protective effect of one allele may outweigh the disease risk in homozygotes.