ABSTRACT
The COVID-19 pandemic has highlighted structural inequalities and racism promoting health disparities among communities of color. Taking cardiovascular disease as an example, we provide a framework for multidisciplinary efforts leveraging translational and epidemiologic approaches to decode the biological impacts of inequalities and racism and develop targeted interventions that promote health equity.
Subject(s)
COVID-19/epidemiology , Health Equity , Health Promotion/methods , Racism , Stress, Physiological/immunology , COVID-19/immunology , COVID-19/metabolism , COVID-19/psychology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/psychology , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Gene Expression Regulation/physiology , Humans , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/physiology , Racism/psychology , Risk Factors , Sympathetic Nervous System/immunology , Sympathetic Nervous System/physiologyABSTRACT
Macrophages comprise a phenotypically and functionally diverse group of hematopoietic cells. Versatile macrophage subsets engage to ensure maintenance of tissue integrity. To perform tissue stress surveillance, macrophages express many different stress-sensing receptors, including purinergic P2X and P2Y receptors that respond to extracellular nucleotides and their sugar derivatives. Activation of G protein-coupled P2Y receptors can be both pro- and anti-inflammatory. Current examples include the observation that P2Y14 receptor promotes STAT1-mediated inflammation in pro-inflammatory M1 macrophages as well as the demonstration that P2Y11 receptor suppresses the secretion of tumor necrosis factor (TNF)-α and concomitantly promotes the release of soluble TNF receptors from anti-inflammatory M2 macrophages. Here, we review macrophage regulation by P2Y purinergic receptors, both in physiological and disease-associated inflammation. Therapeutic targeting of anti-inflammatory P2Y receptor signaling is desirable to attenuate excessive inflammation in infectious diseases such as COVID-19. Conversely, anti-inflammatory P2Y receptor signaling must be suppressed during cancer therapy to preserve its efficacy.
Subject(s)
Inflammation/immunology , Macrophages/immunology , Receptors, Purinergic P2Y/metabolism , Stress, Physiological/immunology , Animals , COVID-19/blood , COVID-19/immunology , Humans , Immunologic Surveillance/drug effects , Immunologic Surveillance/immunology , Inflammation/blood , Inflammation/drug therapy , Macrophages/metabolism , Mice , Neoplasms/blood , Neoplasms/drug therapy , Neoplasms/immunology , Purinergic P2Y Receptor Agonists/pharmacology , Purinergic P2Y Receptor Agonists/therapeutic use , Purinergic P2Y Receptor Antagonists/pharmacology , Purinergic P2Y Receptor Antagonists/therapeutic use , Receptors, Tumor Necrosis Factor/metabolism , STAT1 Transcription Factor/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology , Tumor Necrosis Factor-alpha/metabolism , COVID-19 Drug TreatmentABSTRACT
NASA implements required medical tests and clinical monitoring to ensure the health and safety of its astronauts. These measures include a pre-launch quarantine to mitigate the risk of infectious diseases. During space missions, most astronauts experience perturbations to their immune system that manifest as a detectable secondary immunodeficiency. On return to Earth, after the stress of re-entry and landing, astronauts would be most vulnerable to infectious disease. In April 2020, a crew returned from International Space Station to NASA Johnson Space Center in Houston, Texas, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Post-flight quarantine protocols (both crew and contacts) were enhanced to protect this crew from SARS-CoV-2. In addition, specific additional clinical monitoring was performed to determine post-flight immunocompetence. Given that coronavirus disease 2019 (COVID-19) prognosis is more severe for the immunocompromised, a countermeasures protocol for spaceflight suggested by an international team of scientists could benefit terrestrial patients with secondary immunodeficiency.