Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues.

Autism spectrum disorder (ASD) involves a complex interplay of both genetic and environmental risk factors, with immune alterations and synaptic connection deficiency in early life. In the past decade, studies of ASD have substantially increased, in both humans and animal models. Immunological imbalance (including autoimmunity) has been proposed as a major etiological component in ASD, taking into account increased levels of proinflammatory cytokines observed in postmortem brain from patients, as well as autoantibody production. Also, epidemiological studies have established a correlation of ASD with family history of autoimmune diseases; associations with major histocompatibility complex haplotypes and abnormal levels of immunological markers in the blood. Moreover, the use of animal models to study ASD is providing increasing information on the relationship between the immune system and the pathophysiology of ASD. Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity.

The thymus gland is a central lymphoid organ in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected thymocytes to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, formed of epithelial cells, macrophages, dendritic cells, fibroblasts, and extracellular matrix components. Various interactions occurring between microenvironmental cells and differentiating thymocytes are under neuroendocrine control. In this review, we summarize data showing that thymus physiology is pleiotropically influenced by hormones and neuropeptides. These molecules modulate the expression of major histocompatibility complex gene products by microenvironmental cells and the extracellular matrix-mediated interactions, leading to enhanced thymocyte adhesion to thymic epithelial cells. Cytokine production and thymic endocrine function (herein exemplified by thymulin production) are also hormonally controlled, and, interestingly in this latter case, a bidirectional circuitry seems to exist since thymic-derived peptides also modulate hormonal production. In addition to their role in thymic cell proliferation and apoptosis, hormones and neuropeptides also modulate intrathymic T cell differentiation, influencing the generation of the T cell repertoire. Finally, neuroendocrine control of the thymus appears extremely complex, with possible influence of biological circuitry involving the intrathymic production of a variety of hormones and neuropeptides and the expression of their respective receptors by thymic cells.

Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial–immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre- and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

Undernutrition remains a major issue in global health. Low protein-energy consumption, results in stunting, wasting and/or underweight, three deleterious forms of malnutrition that affect roughly 200 million children under the age of five years. Undernutrition compromises the immune system with the generation of various degrees of immunodeficiency, which in turn, renders undernourished individuals more sensitive to acute infections. The severity of various infectious diseases including visceral leishmaniasis (VL), influenza, and tuberculosis is associated with undernutrition. Immunosuppression resulting from protein-energy undernutrition severely impacts primary and secondary lymphoid organs involved in the response to related pathogens. The thymus—a primary lymphoid organ responsible for the generation of T lymphocytes—is particularly compromised by both undernutrition and infectious diseases. In this respect, we will discuss herein various intrathymic cellular and molecular interactions seen in undernutrition alone or in combination with acute infections. Many examples illustrated in studies on humans and experimental animals clearly revealed that protein-related undernutrition causes thymic atrophy, with cortical thymocyte depletion. Moreover, the non-lymphoid microenvironmental compartment of the organ undergoes important changes in thymic epithelial cells, including their secretory products such as hormones and extracellular matrix proteins. Of note, deficiencies in vitamins and trace elements also induce thymic atrophy. Interestingly, among the molecular interactions involved in the control of undernutrition-induced thymic atrophy is a hormonal imbalance with a rise in glucocorticoids and a decrease in leptin serum levels. Undernutrition also yields a negative impact of acute infections upon the thymus, frequently with the intrathymic detection of pathogens or their antigens. For instance, undernourished mice infected withLeishmania infantum(that causes VL) undergo drastic thymic atrophy, with significant reduction in thymocyte numbers, and decreased levels of intrathymic chemokines and cytokines, indicating that both lymphoid and microenvironmental compartments of the organ are affected. Lastly, recent data revealed that some probiotic bacteria or probiotic fermented milks improve the thymus status in a model of malnutrition, thus raising a new field for investigation, namely the thymus-gut connection, indicating that probiotics can be envisioned as a further adjuvant therapy in the control of thymic changes in undernutrition accompanied or not by infection.