Millions of microorganisms make up the complex microbial ecosystem found in the human gut. The immune system\'s interaction with the gut microbiota is essential for preventing inflammation and maintaining intestinal homeostasis. Numerous metabolic products that can cross-talk between immune cells and the gut epithelium are metabolized by the gut microbiota. Traumatic injury elicits a great and multifaceted immune response in the minutes after the initial offense, containing simultaneous pro- and anti-inflammatory responses. The development of innovative therapies that improve patient outcomes depends on the gut microbiota and immunological responses to trauma. The altered makeup of gut microbes, or gut dysbiosis, can also dysregulate immunological responses, resulting in inflammation. Major human diseases may become more common as a result of chronic dysbiosis and the translocation of bacteria and the products of their metabolism beyond the mucosal barrier. In this review, we briefly summarize the interactions between the gut microbiota and the immune system and human disease and their therapeutic probiotic formulations. We also discuss the immune response to traumatic injury.

The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as \'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer\'s disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a significant health burden. There is an essential need for novel biomarkers and therapeutic targets to improve diagnosis and management. Mendelian randomization (MR) was applied to explore causal links between SLE and various biomarkers like immune cells, metabolites, and inflammatory cytokines using multiple databases. Initially, biomarkers significantly associated with SLE were identified. Bidirectional MR helped clarify these relationships, and a two-step mediation MR examined their effects on SLE risk. Intersection analysis was used to identify biomarkers with consistent effects across datasets. Four biomarkers were identified as having significant associations with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI levels [odds ratio (OR), 1.379; 95% confidence interval (CI), 1.180 to 1.613; FDR, 0.046], IL-17A levels (OR, 2.197; 95% CI, 1.412 to 3.418; FDR, 0.044), N-acetyl-aspartyl-glutamate (NAAG) levels (OR, 0.882; 95% CI, 0.831 to 0.936; FDR, 0.030), and ribitol levels (OR, 0.743; 95% CI, 0.644 to 0.857; FDR, 0.012). Bidirectional MR showed an inverse effect of NAAG on IL-17A levels (OR, 0.978; 95% CI, 0.962 to 0.994; p = 0.006). Mediation analysis indicated that NAAG influenced SLE risk both directly (beta =  - 0.108) and indirectly through IL-17A (beta =  - 0.018), highlighting the potential mediating role of IL-17A. After expanding the significance criteria to p < 0.05, intersection analysis across multiple datasets revealed 29 biomarkers with consistent beta directions, including 19 potential risk factors (beta > 0) and 10 protective factors (beta < 0) for SLE. This research has revealed significant genetic associations with SLE and demonstrated that IL-17A mediates the relationship between NAAG levels and SLE risk, highlighting potential new targets for personalized therapeutic interventions. Key Points • This study employs MR to identify significant genetic associations between various biomarkers and SLE, providing novel insights into potential biomarkers and therapeutic targets. • Four key biomarkers were identified as significantly associated with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI, IL-17A, N-acetyl-aspartyl-glutamate (NAAG), and ribitol. • The findings suggest that NAAG levels have a protective effect against SLE, partly mediated through IL-17A, indicating a complex interplay between these biomarkers in the pathogenesis of SLE. • Intersectional analysis across multiple datasets revealed 29 biomarkers with consistent effects on SLE risk, highlighting new directions for future research and potential personalized therapeutic strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner\'s glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner\'s glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner\'s glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner\'s glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

UNASSIGNED: Persistent infections caused by certain viruses and parasites have been associated with multiple diseases and substantial mortality. Heavy metals are ubiquitous environmental pollutants with immunosuppressive properties. This study aimed to determine whether heavy metals exposure suppress the immune system, thereby increasing the susceptibility to persistent infections.
UNASSIGNED: Using data from NHANES 1999-2016, we explored the associations between heavy metals exposure and persistent infections: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C Virus (HCV), Herpes Simplex Virus Type-1 (HSV-1), Toxoplasma gondii (T. gondii), and Toxocara canis and Toxocara cati (Toxocara spp.) by performing logistic regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Mediation analysis was used to determine the mediating role of host immune function in these associations.
UNASSIGNED: Logistic regression analysis revealed positive associations between multiple heavy metals and the increased risk of persistent infections. In WQS models, the heavy metals mixture was associated with increased risks of several persistent infections: CMV (OR: 1.58; 95% CI: 1.17, 2.14), HCV (OR: 2.94; 95% CI: 1.68, 5.16), HSV-1 (OR: 1.25; 95% CI: 1.11, 1.42), T. gondii (OR: 1.97; 95% CI: 1.41, 2.76), and Toxocara spp. (OR: 1.76; 95% CI: 1.16, 2.66). BKMR models further confirmed the combined effects of heavy metals mixture and also identified the individual effect of arsenic, cadmium, and lead. On mediation analysis, the systemic immune inflammation index, which reflects the host\'s immune status, mediated 12.14% of the association of mixed heavy metals exposure with HSV-1 infection.
UNASSIGNED: The findings of this study revealed that heavy metals exposure may increase susceptibility to persistent infections, with the host\'s immune status potentially mediating this relationship. Reducing exposure to heavy metals may have preventive implications for persistent infections, and further prospective studies are needed to confirm these findings.

Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems.

UNASSIGNED: Coronary heart disease is a highly prevalent inflammatory disease caused by coronary atherosclerosis. Numerous studies have revealed that perivascular adipose tissue is closely associated with atherosclerosis. Here, we conducted a comprehensive analysis of long non-coding RNAs and mRNAs differentially expressed in perivascular adipose tissue in patients with coronary heart disease.
UNASSIGNED: We conducted Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes. Furthermore, single sample gene set enrichment analysis, immune infiltration analysis, and co-expression analysis of differentially expressed long non-coding RNAs and immune gene sets were performed. Finally, the starBase and miRTarBase databases were used to construct a competing endogenous RNA network.
UNASSIGNED: The results show that aortic perivascular adipose tissue has higher inflammation and immune infiltration levels in patients with coronary heart disease. Dysregulated long non-coding RNAs may be related to immunity, inflammation, and hypoxia.
UNASSIGNED: The findings of this study provide new insights into atherosclerosis and coronary heart disease.

Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.