RESUMO
The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4-6. Here we show that a peripheral immune insult strongly activates the body-brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.
Assuntos
Encéfalo , Citocinas , Inflamação , Neuroimunomodulação , Animais , Feminino , Masculino , Camundongos , Encéfalo/citologia , Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Neurônios/fisiologia , Nervo Vago/citologia , Nervo Vago/fisiologia , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.
Assuntos
Lesões Encefálicas Traumáticas , Meninges , Doenças Neuroinflamatórias , Lesões Encefálicas Traumáticas/imunologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Humanos , Animais , Meninges/imunologia , Meninges/patologia , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologia , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologiaRESUMO
BACKGROUND: More than a century ago, experimental work and clinical observations revealed the functional communication between the brain and the peripheral immune system. This is documented on the one hand by studies first demonstrating the effects of catecholamines on the circulation of leukocytes in experimental animals and humans, and on the other hand via the work of Russian physiologist Ivan Petrovic Pavlov and his coworkers, reporting observations that associative learning can modify peripheral immune functions. This work later fell into oblivion since little was known about the endocrine and immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. SUMMARY: In this article, we embark on a fascinating exploration of the historical trajectory of behaviorally conditioned immune responses. KEY MESSAGE: We will pay homage to the visionary scientists who laid the groundwork for this field of research, tracing its evolution from early theories of how associative learning can affect immunity to the modern-day insights that behavioral conditioning of pharmacological responses can be exploited to improve the efficacy of medical interventions for patients.
Assuntos
Aprendizagem por Associação , Humanos , Animais , História do Século XX , História do Século XXI , Aprendizagem por Associação/fisiologia , Sistema Imunitário/fisiologia , Sistema Imunitário/imunologia , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologiaRESUMO
BACKGROUND: Establishing causal relationships is essential in biology and medicine. However, various notions of causality have been operationalized at different times in various fields of the life and health sciences. While this is expected from a history or sociology of science point of view, as different accounts may correspond to what is valued in terms of establishing causal relationships at different times as well as in different fields of biology and medicine, this may come as a surprise for a present-day actor in those fields. If, over time, causal accounts have not been fully dismissed, then they are likely to invite some form of, potentially salutary, explanatory pluralism. SUMMARY: In the decades following WWII, psychosomatic medicine could propose that psychological factors cause somatic diseases. But today, most medicine has to meet the standard of a randomized clinical trial before any causal relationship can be proposed. Instead, in biology, mechanisms seem to be the most-valued causal discourse to explain how phenomena of interest are brought about. Here, the focus will be on how psychoneuroimmunology, an interdisciplinary research field addressing interactions between the nervous system and immune system, and between behavior and health, has considered causal relationships between psychological factors and cancer. KEY MESSAGES: When it comes to causal explanations of links between psychological factors and cancer, psychoneuroimmunology is invited to consider the question of the directionality of these links as well as what and how factors causally contribute to cancer.
Assuntos
Neoplasias , Neuroimunomodulação , Psiconeuroimunologia , Medicina Psicossomática , Humanos , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologia , Neoplasias/imunologia , Neoplasias/psicologia , História do Século XX , CausalidadeRESUMO
BACKGROUND: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. SUMMARY: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease. KEY MESSAGES: During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.
Assuntos
Encéfalo , Doença de Chagas , Timo , Humanos , Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Animais , Encéfalo/imunologia , Timo/imunologia , Timo/fisiologia , Trypanosoma cruzi/fisiologia , Trypanosoma cruzi/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Cardiovascular diseases are the leading cause of death worldwide. Pathophysiologically, metabolic and inflammatory processes contribute substantially to the development and progression of cardiovascular diseases. Over the past decade, the role of disease-propagating inflammatory processes has been strengthened and reframed, leading to trials testing anti-inflammatory drugs for the treatment of atherosclerosis and its complications. Despite these achievements, further research in both pre-clinical and clinical studies is warranted to explore new targets, to better identify responders, and to refine therapy strategies to combat inflammation in human disease. Environmental disturbances, so-called lifestyle-associated cardiovascular risk factors, greatly alter the immune system in general and leukocytes in particular, thus affecting the progression of atherosclerosis. Epidemiological studies have shown that exposure to mental stress can be closely linked to the occurrence of cardiovascular disease. Here, we describe how acute and chronic mental stress alter the immune system via neuroimmune interactions, thereby modifying vascular inflammation. In addition, we identify gaps that still need to be addressed in the future.
Assuntos
Neuroimunomodulação , Estresse Psicológico , Humanos , Estresse Psicológico/imunologia , Estresse Psicológico/complicações , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Inflamação/imunologia , Modelos Imunológicos , Doenças Cardiovasculares/imunologia , Aterosclerose/imunologiaRESUMO
The evaluation of the neuroimmunoepidemiological response from the reibergram allows the determination of the specific antibody index for a determined etiological agent. This evaluation has served to know the behavior of the neuroimmune response in pediatric patients to different herpesviruses, evaluate the effectiveness of vaccination campaigns and find a response that helps in the diagnosis of various processes that affect this system(AU)
Assuntos
Humanos , Neuroimunomodulação/imunologiaRESUMO
El estrés se define como el estado de alarma de los organismos ante diversos desafíos. La Psiconeuroendocrinoinmunología es una ciencia que integra la psiquis, el sistema nervioso, endocrino e inmune; y estudia las múltiples y complejas interrelaciones entre ellos lo cual permite tratar de manera integral el proceso salud-enfermedad. La alteración del equilibrio entre la psiquis y los sistemas mencionados puede ocasionar daños al organismo como es el caso de algunas enfermedades reumatológicas(AU)
Stress is defined as the state of alarm of living beings in case of various challenges. Psycho-neuro-endocrine-immunology is a science that integrates the psyche with the nervous, endocrine and immune systems. It studies the multiple and complex interrelations among them, which allows us to deal comprehensively with the health-disease process. The alteration if the balance between the psyche and the aforementioned systems can cause damage to the organism, as in the case of some rheumatologic diseases(AU)
Assuntos
Humanos , Alergia e Imunologia , Sistema Nervoso , Estresse Psicológico/epidemiologia , Neuroimunomodulação/imunologia , Processo Saúde-DoençaRESUMO
Estrés es un concepto científico que se refiere a la respuesta inespecífica del organismo frente a cualquier demanda, en la cual la capacidad de adaptación individual constituye el factor más importante. Los sistemas nervioso, endocrino e inmune están en estrecha interrelación y hoy en día la célula inmune puede considerarse un órgano sensorial ya que es capaz de responder tanto a estímulos físicos como psíquicos. Se revisan las características del sistema inmune, la red neuroinmunoendocrina y los mecanismos de neuro-inmuno-modulación. El estudio de la inmunidad celular en la depresión se ha abordado, in vitro, a través del recuento de células, de la proliferación de linfocitos mediante mitógenos y de la actividad de las células natural killer. En pacientes, in vivo, se ha determinado la respuesta cutánea de hipersensibilidad retardada. Los resultados en general han sido contradictorios ya que existen reparos metodológicos y diversos factores; edad, gravedad del cuadro depresivo, hospitalización, trastornos del sueño, baja de peso, que dificultan las conclusiones definitivas. Las alteraciones en la función noradrenégica o en el eje hipotálamo-hipófisis-adrenal pudieran explicar algunos casos de deterioro de la inmunidad en la depresión
Assuntos
Humanos , Imunidade Celular/imunologia , Depressão/imunologia , Estresse Psicológico/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Neuroimunomodulação/imunologia , Sistema Hipotálamo-Hipofisário/imunologiaRESUMO
A partir de la década de los setentas se ha demostrado una importante dependencia direccional entre los sistemas inmune (SI) y el sistema nervioso central (SNC), con la intervención de mensajeros comunes. Las citocinas del SI son capaces de modular respuestas y procesos a nivel del SNC, mientras que los neurotransmisores y neuropéptidos pueden a su vez ejercer su efecto sobre grupos celulares especificos del SNC. Un grupo importante de estos péptidos es el de los opioides endógenos, como las endorfinas y las encefalinas. Las endorfinas alfa y beta tienen la capacidad de activar la quimiotaxis e influenciar la diferenciación y proliferación de linfocitos T y B. La ß-endorfina incrementa la actividad de las células natural killer (NK). La met-encefalina y la leu-encefalina desarrollan funciones de tipo inmunomodulador con respecto a la producción de anticuerpos (Acs) por las células plasmáticas. Incrementan la producción de Acs., pueden aumentar el número de leucocitos circulantes y la producción de interleucina-2 (IL-2). Una vía en el sistema neuroinmunológico es controlada por el eje-HPA (hipotálamo-pituitaria-adrenales, principal coordinador y regulador de las interacciones entre el sistema inmune, el SNC y el endocrino