Neuroimmunomodulation最新文献

Introduction: Allergies are an increasingly widespread health problem and prior evidence suggests that psychological factors are involved in their occurrence and alleviation. This study aimed to investigate how placebo treatment can reduce type-I allergic symptoms in a skin prick-test in healthy volunteers.

Methods: Healthy volunteers of all genders were included in the study (N = 88) and were randomized into three groups. i) A classically conditioned group receiving the anti-histaminergic drug cetirizine as unconditioned stimuls (US) and a novel gustatory stimulus as conditioned stimulus (CS), ii) a context-control group receiving cetirizine (US) and water as CS and iii) an open-label placebo group. In the spirit of ethical application of placebo, participants were not blinded with regard to the study question. Histamine skin prick-tests were conducted at baseline, after five acquisition trials, before evocation as well as after three and five evocation trials. Self-rated itch and wheal size measurements served as outcome parameters.

Results: Itch was significantly reduced after medication and (open) placebo intake. Wheal size was only reduced significantly after medication intake during acquisition. After 9 days of wash-out, itch ratings were lower in participants who had received open-label placebo compared to those who had initially received cetirizine. During the evocation week, the decline in wheal size did not reach statistical significance and there was no significant differential effect of group allocation. Reported expectations of symptom relief at the last visit correlated positively with reductions of wheal size.

Conclusion: These results support the theory that treatment expectations correlate with reductions in allergic skin symptoms. Participants of all groups experienced a reduction in itch, while wheal size was only reduced in those participants with high expectations, based on prior experiences and group allocation. Future studies should investigate the underlying neuropsychological mechanisms of these expectation-induced anti-histaminergic effects.

Background: Aging is associated with enumerative and functional changes of peripheral innate immune cells, notably myeloid cells (ex., monocytes/macrophages and neutrophils). Peripheral myeloid cells routinely infiltrate the brain, particularly at the brain borders, influencing cognition, mood, and stress responses.

Summary: Here, we review how the dysfunctional crosstalk between circulating myeloid cells and brain cells may contribute to the development of late-life depression and Alzheimer's disease during aging. The aged cerebral microglia (i.e., resident macrophages) exhibit dystrophic morphology and impaired phagocytosis while peripheral myeloid cells expand in number but display functional deficits, including impaired phagocytosis and pro-inflammatory biased response. The peripheral myeloid changes collectively contribute to systemic chronic inflammation and tissue dysfunction. Epigenetic changes and metabolic disruptions, such as altered glucose utilization, exacerbate pro-inflammatory states.

Key messages: The cumulative impact of these alterations undermines neuroprotection and facilitates age-related neuropsychiatric conditions, including neurodegenerative diseases and late-life depression. The identification of pro-aging circulating factors and cells could pave the way for new therapeutic strategies aimed at mitigating cognitive decline and improving mood. Targeting myeloid cell metabolism or inflammatory signaling pathways emerges as a promising strategy to mitigate aging-associated neuropsychiatric syndromes.

Pneumonia is an infection that affects the alveolar spaces of the lungs, associated with high global mortality, and remains a significant public health challenge worldwide. In a compromised immune system, the infection can progress, leading to the establishment of pneumonia. During this process, an intense inflammatory response is triggered in the lungs through the activation of resident immune cells, especially alveolar macrophages. This activation promotes the recruitment of neutrophils and the release of proinflammatory cytokines, ultimately resulting in the formation of exudative infiltrates within the alveoli. Pneumonia is a leading cause of sepsis, particularly among hospitalized patients and in intensive care units. Sepsis represents one of the most severe complications of pneumonia and is characterized by a dysregulated systemic inflammatory response to lung infection. Another critical challenge to treating clinical infectious conditions, which can lead to life-threatening sepsis, septic shock, and multi-organ dysfunction, is the continuous growth of antimicrobial resistance (AMR) in bacteria. Among the organ dysfunctions associated with sepsis, sepsis-associated encephalopathy (SAE) is the most frequent and constitutes a primary contributor to the neurological alterations observed in critically ill patients. Although SAE is often classified as a fully reversible pathophysiological process, increasing evidence suggests an association between sepsis, structural brain injury, and long-term neurological sequelae. The central nervous system (CNS) is one of the first regions exposed to peripheral inflammation during sepsis, allowing inflammatory mediators and immune cells to infiltrate the brain. This process activates microglia, the resident immune cells of the CNS, exposing neurons to an oxidative stress-rich environment that leads to neuronal dysfunction and apoptosis. A dysregulated proinflammatory microglial response plays a significant role in SAE, as microglia-derived cytokines are strongly associated with neuronal damage. Furthermore, activated microglia stimulate astrocytes to adopt a reactive inflammatory phenotype, thereby amplifying neuroinflammation. Recent studies have demonstrated that regulating microglial and astrocytic hyperactivation can attenuate the inflammatory response. Therefore, targeting glial cells during SAE holds significant therapeutic potential, offering a promising avenue for the development of new strategies aimed at reversing the exacerbated CNS inflammatory response, mitigating neuronal damage, and ultimately reducing the long-term neurological sequelae observed in post-septic patients.

Background: Tuberculosis (TB) remains a leading cause of mortality worldwide among infectious agents, and HIV increases the risk of developing into active disease. HIV-TB coinfection impairs immune responses, while chronic inflammation and infection-associated stress activate neuroendocrine pathways that deeply impact immune homeostasis. Adrenal steroids such as cortisol, dehydroepiandrosterone (DHEA) and its metabolites, along with metabolic hormones like leptin and adiponectin, have emerged as critical regulators of immune function, although their role in TB pathogenesis, particularly in co-infected individuals, remains underexplored.

Summary: This review navigates over current evidence on the neuroendocrine-immune crosstalk in HIV-TB coinfection, focusing on adrenal and metabolic hormonal axes. We first summarize how HIV-driven CD4+ T cell depletion, chronic immune activation, and altered granuloma dynamics predispose individuals to TB reactivation. We then examine findings indicating that TB and HIV disrupt hypothalamic-pituitary-adrenal (HPA) axis homeostasis, leading to elevated cortisol levels, reduced DHEA and its metabolites, and an unfavorable cortisol/DHEA ratio, which correlated with poor immune control and disease severity. Preclinical studies highlight immunomodulatory properties of DHEA derivatives, such as 7-oxo-DHEA (7-OD), which restore Th1 responses, limit Treg expansion, and enhance macrophage antimicrobial activity. Metabolic hormones, particularly leptin and adiponectin, further shape host immunity and energy allocation; their dysregulation in coinfection contributes to wasting, impaired granuloma formation, and increased immune reconstitution inflammatory syndrome (IRIS) risk. Despite compelling preclinical findings, clinical studies on hormonal modulation remain scarce, emphasizing the need for translational research that links endocrinology and infectious disease immunology.

Key messages: HIV-TB coinfection creates a neuroendocrine-immune imbalance, with dysregulation of the HPA axis and metabolic hormones contributing to impaired immune control and accelerated disease progression. Adrenal hormones such as DHEA and its metabolite 7-oxo-DHEA show potential as immunomodulatory agents, capable of restoring Th1 responses, limiting Treg expansion, and supporting host-directed therapies. Additionally, leptin and adiponectin emerge as crucial metabolic players that integrate nutritional status and immune activity and may serve as potential biomarkers for TB management. Altogether, integrating endocrine profiling into TB research and advancing the clinical evaluation of hormonal immunomodulators may unlock novel avenues for precision medicine, improving treatment strategies for populations affected by the HIV and TB epidemics.

Background: Although this seems to be common knowledge among experts, it is important to remind readers that two populations, namely, brain microglia and macrophages, found in different compartments of the central nervous system, play essential roles in innate neuroimmunology.

Summary: Here, some historical and conceptual background will be provided that should allow the reader to place recent findings on these cells in some context and perspective.

Key messages: It will be argued that (1) the brain is not devoid of immune response, but does represent an immune-privileged site, (2) innate neuroimmunology concerns brain border macrophages and parenchymal microglia, (3) even though brain border macrophages have been less extensively studied than parenchymal microglia, it is progressively becoming clear that these populations play different roles in physiological and pathological conditions and (4) while it is tempting to only use the latest technologies to obtain new findings, it is also essential, for the sake of science, to "triangulate" with findings obtained with more classic approaches. To determine whether and when innate neuroimmune responses are protective or pathological will be an important aim for future research.

Introduction: Inflammation and social relationships are bidirectionally linked, yet evidence in young, nonclinical populations is scarce. Given that elite athletes face continuous immune challenges and unique social conditions, this cohort provides a model to explore this association.

Methods: Several quantile regressions were computed across 422 elite athletes. To account for both the magnitude of inflammation and the characteristics of social relationships, quantiles were determined based on the concentrations of tumor necrosis factor alpha, interleukin-6, and the systemic inflammatory response index (SIRI) as well as on measures of the total, general perceived social support. The corresponding predictors were social support and the inflammatory markers.

Results: A higher total, general perceived social support predicted a significantly lower SIRI in the lowest quartile as well as lower concentrations of the cytokines in the highest three quartiles. Effects were small but robust. Moreover, higher inflammation predicted a lower total, general perceived social support in elite athletes, when the perceived social support was relatively moderate. However, this effect was not robust when covariates, such as urea or the living situation, were added to the models.

Conclusion: Results suggest that elite athletes' social relationships are a small yet important factor influencing the inflammatory response. The social support elite athletes perceive, however, appears to be influenced by inflammation only under specific biopsychosocial conditions.

Neuroimmunology focuses on the two-way communication between the nervous and immune systems, a crucial relationship that maintains the body's internal balance. Disruptions in this neural-immune axis are associated with several disorders. Fatty acids, as bioactive molecules, can modulate both neural and immune functions. Saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) have opposite effects: SFAs promote inflammation and are associated with neurodegenerative diseases and cognitive impairment, whereas PUFAs exhibit anti-inflammatory and neuroprotective properties. The balance between SFAs and PUFAs is key in regulating neuroimmune interactions. Fatty acid receptors act as essential molecular sensors, connecting lipid signaling to both immune and neural outcomes, their activation or inhibition influences cytokine production and neuron survival. Due to their role in these pathways, targeting fatty acid interactions to control inflammation and promote neural repair represents a promising strategy for neurological disease therapies. This review examines how fatty acids influence neuroimmune cells and may pave the way for the development of new therapeutic approaches.

Background: Devoid of a lymphatic system, the central nervous system (CNS) relies primarily on innate immunity for protection. While these immune responses help to fight pathogens, they can also cause irreversible damage because of the CNS's limited regenerative capacity. Therefore, it is crucial to understand which CNS cells contribute to pathogen clearance but in doing so potentially damage surrounding tissue.

Summary: Neurobrucellosis, caused by intracellular bacteria from the genus Brucella, is an inflammatory disease. Recent studies have shown that astrocytes and microglia are the source of this neuro-inflammation. In response to Brucella infection they create a microenvironment in the CNS which leads to the destabilization of the glial structure, the damage of the blood-brain barrier (BBB) and neuronal demise. Using Brucella as an example, this review of CNS glial cells responses to an intracellular bacterium shows how inflammation generates damage on tissue instead of infection resolution.

Key messages: Since the network of pathophysiological interactions described here are not necessarily limited to brucellosis, it is reasonable to assume that these mechanisms could be relevant in other neurological disorders in which inflammation plays a key role.