Innate Immunity System in Patients With Cardiovascular and Kidney Disease.

With a global burden of 844 million, chronic kidney disease (CKD) is now considered a public health priority. Cardiovascular risk is pervasive in this population, and low-grade systemic inflammation is an established driver of adverse cardiovascular outcomes in these patients. Accelerated cellular senescence, gut microbiota-dependent immune activation, posttranslational lipoprotein modifications, neuroimmune interactions, osmotic and nonosmotic sodium accumulation, acute kidney injury, and precipitation of crystals in the kidney and the vascular system all concur in determining the unique severity of inflammation in CKD. Cohort studies documented a strong link between various biomarkers of inflammation and the risk of progression to kidney failure and cardiovascular events in patients with CKD. Interventions targeting diverse steps of the innate immune response may reduce the risk of cardiovascular and kidney disease. Among these, inhibition of IL-1ß (interleukin-1 beta) signaling by canakinumab reduced the risk for cardiovascular events in patients with coronary heart disease, and this protection was equally strong in patients with and without CKD. Several old (colchicine) and new drugs targeting the innate immune system, like the IL-6 (interleukin 6) antagonist ziltivekimab, are being tested in large randomized clinical trials to thoroughly test the hypothesis that mitigating inflammation may translate into better cardiovascular and kidney outcomes in patients with CKD.

The immune enhancement effect of Nelumbo nucifera Gaertner Seed Extract (NSE) in murine macrophage RAW 264.7 cells

Since the global shock caused by COVID-19, interest in immune-enhancing materials is rapidly increasing, therefore, the development of novel materials is necessary from the industrial and health perspectives. In this study, we selected Nelumbo nucifera Gaertner Seed Extract (NSE) and evaluated immune enhancement effect by using RAW 264.7 murine macrophage cells. NSE significantly up-regulated production of nitric oxide and reactive oxygen species without affecting cell viability in RAW 264.7 cells. Additionally, NSE exhibited an increase of inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells. The enzyme-linked immuno-sorbent assay results showed that NSE-treatment significantly enhanced production of interleukin 6 and tumor necrosis factor-α in RAW 264.7 cells. Furthermore, we observed that NSE significantly up-regulated phosphorylation of p65, I kappa B kinase α/β, and I kappa B (IκB) α as well as down-regulation of IκB α expression in RAW 264.7 cells. Our findings indicate that NSE could be the potential health-functional food material with capacity of improving immunity via Nuclear factor-kappa B signaling pathway. © 2023, Korean Society for Applied Biological Chemistry. All rights reserved.

Human T2R38 Bitter Taste Receptor Expression and COVID-19: From Immunity to Prognosis

Background: Bitter taste-sensing type 2 receptor (T2Rs or TAS2Rs) found on ciliated epithelial cells and solitary chemosensory cells have a role in respiratory tract immuni-ty. T2Rs have shown protection against SARS-CoV-2 by enhancing the innate immune response. The purpose of this review is to outline the current sphere of knowledge re-garding this association. Method(s): A narrative review of the literature was done by searching (T2R38 OR bitter taste receptor) AND (COVID-19 OR SARS-CoV-2) keywords in PubMed and google scholar. Result(s): T2R38, an isoform of T2Rs encoded by the TAS2R38 gene, may have a potential association between phenotypic expression of T2R38 and prognosis of COVID-19. Current studies suggest that due to different genotypes and widespread distributions of T2Rs within the respiratory tract and their role in innate immunity, treatment protocols for COVID-19 and other respiratory diseases may change accordingly. Based on the phenotypic expression of T2R38, it varies in innate immunity and host response to respiratory infection, systemic symptoms and hospitalization. Conclusion(s): This review reveals that patients' innate immune response to SARS-COV-2 could be influenced by T2R38 receptor allelic variations.Copyright © 2023, Avicenna Journal of Medical Biotechnology.

Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities.

Pneumonia is inflammation in the lungs, which is usually caused by an infection. The symptoms of pneumonia can vary from mild to life-threatening, where severe illness is often observed in vulnerable populations like children, older adults, and those with preexisting health conditions. Vaccines have greatly reduced the burden of some of the most common causes of pneumonia, and the use of antimicrobials has greatly improved the survival to this infection. However, pneumonia survivors do not return to their preinfection health trajectories but instead experience an accelerated health decline with an increased risk of cardiovascular disease. The mechanisms of this association are not well understood, but a persistent dysregulated inflammatory response post-pneumonia appears to play a central role. It is proposed that the inflammatory response during pneumonia is left unregulated and exacerbates atherosclerotic vascular disease, which ultimately leads to adverse cardiac events such as myocardial infarction. For this reason, there is a need to better understand the inflammatory cross talk between the lungs and the heart during and after pneumonia to develop therapeutics that focus on preventing pneumonia-associated cardiovascular events. This review will provide an overview of the known mechanisms of inflammation triggered during pneumonia and their relevance to the increased cardiovascular risk that follows this infection. We will also discuss opportunities for new clinical approaches leveraging strategies to promote inflammatory resolution pathways as a novel therapeutic target to reduce the risk of cardiac events post-pneumonia.

[Pulmonary innate immune response in Sars-cov-2 infection] / Respuesta inmunitaria innata pulmonar en la infección por Sars-Cov-2

Introduction: The emerging infection caused by the new SARS-CoV-2 coronavirus has become a real challenge for the scientific community. Currently, there is little knowledge about the pathogenesis of COVID-19 and in recent times the participation of the host's own immune response in the progression of the disease has been proposed. Innate pulmonary immunity is the first barrier against different toxins, which can cause tissue damage, with the consequent alteration of respiratory function. However, a loss in the regulation of these inflammatory mechanisms can cause a disruption in the homeostasis of the affected tissue. Objective: To evaluate the role of the pulmonary innate immune response in the pathogenesis of COVID-19. : Results: A global alteration of the pulmonary innate immune response was found in SARS-CoV-2 infection, which would have relevance in the pathogenesis of COVID-19. Materials and methods: A systematic review of studies published in scientific search engines was carried out: PubMed, Google Scholar, Science Direct. The following keywords were used: "COVID-19"; "Acute Respiratory Distress Syndrome"; "SARS-CoV-2"; "Innate pulmonary immunity"; "Innate immune response". Conclusion: The global involvement of the innate immune response and consequently of lung tissue homeostasis, in SARS-CoV-2 infection, requires the design of new therapeutic strategies aimed at modulating the altered pro-inflammatory mechanisms in COVID-19.

Introducción: La infección emergente producida por el nuevo coronavirus SARS-CoV-2, se ha constituido en un verdadero desafío para la comunidad científica. Actualmente, es escaso el conocimiento acerca de la patogenia de COVID-19 y en el último tiempo, se ha propuesto la participación de la respuesta inmunitaria propia del huésped, en la progresión de la enfermedad. La inmunidad innata pulmonar se constituye como la primera barrera ante diferentes noxas, que puedan provocar lesión tisular, con la consiguiente alteración de la función respiratoria. Sin embargo, una pérdida en la regulación de estos mecanismos inflamatorios puede provocar una disrupción en la homeostasis del tejido afectado. Objetivo: Evaluar el papel de la respuesta inmune innata pulmonar en la patogenia de COVID-19. Materiales y métodos: Se realizó una revisión sistemática de estudios publicados en buscadores científicos: PubMed, Google Scholar, Science Direct. Se utilizaron las siguientes palabras claves: "COVID-19"; "Acute Respiratory Distress Syndrome"; "SARS-CoV-2"; "Innate pulmonary immunity"; "innate immune response". Resultados: Se encontró una alteración global de la respuesta inmune innata pulmonar en la infección por SARS-CoV-2, que tendría relevancia en la patogenia de COVID-19. Conclusión: La afectación global de la respuesta inmune innata y por consiguiente de la homeostasis tisular pulmonar, en la infección por SARS-CoV-2, requiere el diseño de nuevas estrategias terapéuticas destinadas a la modulación de los mecanismos pro inflamatorios alterados en COVID-19.

Innate Immune Stimulation Should not be Overlooked in Post-exposure Prophylaxis and Early Therapy for Coronavirus Infections.

We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

Associations between markers of cellular and humoral immunity to rubella virus following a third dose of measles-mumps-rubella vaccine.

INTRODUCTION: Rubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual's response to a third dose of the vaccine. METHODS: Healthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes. RESULTS: High and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1ß, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders. CONCLUSION: IL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.