Neuroimmunomodulation最新文献

Introduction: Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gut microbiome and common mental disorders in European, North American, and Asian populations. As part of the saNeuroGut Initiative, we assessed associations between gut microbial composition and self-reported symptoms of anxiety, depression, and posttraumatic stress (PTS) among South African adults.

Methods: Participants completed validated, online self-report questionnaires to evaluate symptoms of state anxiety, trait anxiety, depression, and PTSD. Eighty-six stool-derived microbial DNA samples underwent sequencing of the V4 region of the 16S rRNA gene to characterise gut bacterial taxa in the sample.

Results: No significant associations were observed between symptom severity scores and alpha (Shannon and Simpson indices) and beta (Aitchison distances) diversity metrics. Linear regression models revealed that the abundances of Catenibacterium, Collinsella, and Holdemanella were significantly positively associated with the severity of PTS symptoms.

Conclusion: Catenibacterium, Collinsella, and Holdemanella have each previously been associated with various psychiatric disorders, with Catenibacterium having been positively associated with symptoms of PTSD in another South African cohort. This study sheds light on the relationship between the human gut microbiome and symptoms of anxiety, depression, and PTS in a South African adult sample.

Background: The gut microbiota is increasingly recognized as a critical regulator of brain function, influencing neurodevelopment, brain physiology, and disease vulnerability in part through its interactions with microglia, the resident immune cells of the central nervous system. Microbial metabolites, beginning prenatally and persisting throughout the lifespan, modulate fundamental aspects of microglial biology.

Summary: Microglia from germ-free mice exhibit persistent immaturity, altered energy metabolism, and blunted inflammatory responses, which can be partially reversed by microbial colonization or supplementation with specific bacterial metabolites. Short-chain fatty acids, tryptophan-derived indoles, and secondary bile acids have emerged as key microbial mediators that regulate microglial development, metabolism, and immune function, whereas certain inflammatory metabolites, such as trimethylamine n-oxide, disrupt microglial homeostasis, and worsen neurodegeneration.

Key messages: These findings reveal distinct metabolite-driven pathways linking microbial composition to microglial phenotypes, positioning the microbiome as a potential key influencer of neurodevelopmental trajectories and the pathophysiology of psychiatric and neurological disorders. Despite recent advances, major knowledge gaps persist in understanding the precise molecular intermediaries and mechanisms through which metabolite signaling to microglia shapes susceptibility or resilience to brain-based disorders. Understanding both the bacterial metabolomic landscape and its collective impact on microglial programming holds substantial therapeutic promise, offering avenues to target microbial metabolite production or administer them directly to modulate disease susceptibility.

Introduction: Thyroid hormone homeostasis during pregnancy is crucial for proper neurodevelopment and cognitive capacity during adulthood. Accumulating evidence reveals that gestational hypothyroxinemia (HTX) modulates the immune response of the adult offspring.

Methods: In the present study, adult mice gestated in HTX and their euthyroid counterparts were induced with a mild form of experimental autoimmune encephalomyelitis (EAE), a widespread model of multiple sclerosis, and analyzed at baseline and 7 days after EAE induction.

Results: Levels of circulating IL-17 were significantly lower in mice gestated in HTX at both timepoints, while circulating IFN-γ was significantly higher only in mice gestated in HTX, 7 days after EAE induction. A significant increase in type 1 innate lymphoid cells (ILC1) was found only in mice gestated in HTX 7 days after EAE induction, while type 3 innate lymphoid cells (ILC3) populations showed no variation. Interestingly, a significant increase of Th17 CD4+ cells was found only in mice of euthyroid gestation, 7 days after EAE induction.

Conclusion: These results highlight the repercussions of thyroid hormone impairment in utero at adult ages while dissecting on the pathogenesis of EAE in terms of Th1/Th17 balance from an innate immune perspective. These findings contribute to the advancement of our comprehension of the presymptomatic stage of EAE, unveiling new paths for basic and translational research in the field of neuroinflammation.

Background: Postoperative cognitive dysfunction (POCD) affects 10-54% of surgical patients, especially the elderly. It is increasingly recognized as a major perioperative complication driven by neuroinflammatory mechanisms. While physiological postoperative inflammation supports wound healing and recovery, pathological hyperactivation of immune pathways leads to blood-brain barrier disruption, immune cell infiltration, and long-term cognitive impairment.

Summary: This review examines the contribution of innate and adaptive immune cell subsets to POCD pathogenesis. Activated microglia, infiltrating monocytes, and neutrophils initiate neuroinflammatory cascades through cytokine release, while dysregulated T-cell balance (increased Th17 cells, reduced regulatory T cells) exacerbates dysfunction. Key molecular pathways involve damage-associated molecular patterns, complement activation, and impaired neurotrophin signaling. Clinical biomarkers such as IL-6, TNF-α, and S100B show predictive value, with sensitivity of 65-85% and specificity of 75-90%. Current therapeutic strategies include dexmedetomidine, anti-inflammatory agents, and comprehensive perioperative optimization.

Key messages: POCD is a frequent postoperative complication linked to immune dysregulation and neuroinflammation. Both innate and adaptive immune cells play central roles, with microglial polarization and T-cell imbalance as major drivers. Biomarkers such as IL-6, TNF-α, and S100B can support risk stratification and early intervention. Immunomodulatory therapies and perioperative optimization represent promising approaches to reduce POCD incidence and improve patient outcomes.

Background: For over 130 years, scientists have been suggesting that infection and inflammation may play a role in psychosis and other psychiatric disorders. First attempts to treat psychosis by immune-modulating therapies were made early in the last century; however, after the development of antipsychotics in the 1950s, scientific interest shifted away from immunological aspects of psychiatric disorders to the involvement of catecholamines, in particular dopamine, in psychosis.

Summary: Antipsychotic treatment was not as successful as expected, so the 1990s saw renewed interest in inflammation and psychoneuroimmunological research in schizophrenia and beyond. In parallel, advances in immunological research methods allowed immunological and inflammatory mechanisms to be studied in more detail.

Key messages: Clinical studies and meta-analyses have demonstrated positive effects of anti-inflammatory treatment in certain patients with psychiatric disorders. More research is needed to elucidate exactly how immunological mechanisms result in disease pathophysiology, with the aim to improve anti-inflammatory and personalized treatments.

Introduction: Little is known about the effects of a positive human-animal relationship on animal health and resilience. This study investigated the effects of regular positive human-animal interactions on pigs' response to an immune challenge.

Methods: Twenty-four female pigs were recruited at weaning (5 weeks old), and siblings of similar weights were allocated to either the positive contact treatment with positive contacts given by a human to groups of 3 pigs in their home pen or the control treatment only exposed to a human standing immobile and silently in front and outside their home pen. Treatment sessions were applied over 9 consecutive weeks, lasted 10 min per group, and occurred twice daily (morning and afternoon), 3 days a week. At 16 weeks of age, pigs were submitted to an immune challenge, which consisted of a single intravenous administration of lipopolysaccharide (LPS; 2 µg/kg). The sickness behaviours of pigs were observed using scan sampling every 5 min over 6 h post-administration, recording somnolence, vomiting, diarrhoea, cramping, shivering, and panting. Blood samples were taken before the LPS administration, after 1 h and 3 h. Blood plasma was analysed to quantify tumour necrosis factor alpha, interleukins 6 and 10, immunoglobulin A, and cortisol concentrations, and blood serum was analysed to quantify a brain-derived neurotrophic factor. Behavioural and physiological data were statistically analysed using general linear models in R.

Results: Both treatments showed signs of sickness behaviour following LPS administration, but the two treatments did not differ in the frequency, severity of sickness behaviours, or length of recovery or in the blood plasma concentration of cytokines and cortisol measured.

Conclusion: Therefore, regular exposure to positive contacts with a human over several weeks, although leading to the development of a positive human-animal relationship, did not enhance the pigs' response to this immune challenge or the immune parameters measured in this study.

Background: Parasitic infections of the central nervous system (CNS) represent a considerable health burden in low- and middle-income countries. During chronic disease, parasites modulate host immunity to ensure long-term persistence while limiting collateral tissue damage. A key feature of this immune remodeling is the progressive T-cell dysfunction that may culminate in T-cell exhaustion, characterized by increased expression of inhibitory receptors (TIM-3, LAG-3, KLRG1), checkpoint molecules (PD-1, PD-L1), suppressor of cytokine signaling-1 (SOCS1), and arginase-1.

Summary: The relevance of the neuroimmune-endocrine (NIE) axis on the modulation of T-cell dysfunction related to parasite survival needs to be explored. This review focuses on two parasitic CNS infections: neurotoxoplasmosis induced by the intracellular protozoan Toxoplasma gondii and neurocysticercosis caused when cysticercus of the cestode Taenia solium lodges in the CNS.

Key messages: We present updated evidence on how these phylogenetically distant pathogens exploit the NIE network, describe the physiological consequences for the host, and highlight shared and distinct mechanisms behind T-cell exhaustion. Finally, we address emerging immunotherapeutic strategies aimed at reversing exhaustion and restoring protective immunity.

Background: Folliculostellate (FS) cells are non-endocrine cells of the anterior pituitary with roles in local communication, immune-endocrine regulation, and tissue homeostasis. Although they comprise only a small fraction of the gland, FS cells exert paracrine influence on hormone-secreting cells and respond to immune signals, particularly through interleukin-6 production.

Summary: This review outlines classical and newly described features of FS cells, and we also examine their dual role in pituitary tumorigenesis, where they may both promote and restrain tumor growth depending on context. FS cells act as immune sensors, mediating responses to bacterial signals and modulating the hypothalamic-pituitary-adrenal axis during stress and aging.

Key messages: Their potential contribution to inflammaging and tumor progression highlights FS cells as key players in pituitary physiology and pathology and immune-neuroendocrine connections.

Introduction: Major depressive disorder (MDD) is one of the most prevalent mental disorders associated with various negative impacts such as lower overall quality of life, increased morbidity risk, and even premature mortality. According to the biopsychosocial model of health and disease, multiple factors contribute to the development and manifestation of MDD. Here, we assessed preselected social, psychological, and biological variables and tested their power to predict MDD diagnosis using logistic regression models.

Methods: In 24 patients with current MDD diagnosis and 35 healthy control participants, the following variables were measured to test for associations with MDD diagnosis: (1) emotional neglect and adult attachment style as social variables, (2) thought suppression and cognitive reappraisal as psychological variables, and (3) mitochondrial density (citrate synthase activity as a surrogate marker of mitochondrial density) measured in peripheral blood mononuclear cells (PBMCs) as a biological variable.

Results: The following biopsychosocial variables were associated with MDD diagnosis. Participants with greater emotional neglect (OR: 1.273, 95% CI: 1.059-1.645), higher levels of intrusive thoughts (OR: 1.738, 95% CI: 1.282-3.066), and decreased mitochondrial density in PBMCs (OR: 0.298, 95% CI: 0.083-0.784) had a higher probability of belonging to the MDD group.

Conclusions: In line with biopsychosocial models of depression, the present results indicate that variables at different levels of analysis are conjointly related to MDD. These findings open new perspectives for the diagnosis and treatment of MDD, but they need to be replicated in larger samples in the future.