Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart

Circulation, Ahead of Print. BACKGROUND:Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation.METHODS:We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2–associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor.RESULTS:In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2+(C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor α–neutralizing antibody reduced cardiac monocytes and inflammatory MHCIIloCCR2+macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure.CONCLUSIONS:Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2+macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

Leggi
Marzo 2024

New facet of CARs: HBV-specific CARs as inhibitors of virus morphogenesis and release

Although safe and effective vaccines against HBV (hepatitis B virus) are available, there are worldwide more than 2 billion people who had an HBV infection and about 250 million people suffering from chronic HBV infection. Chronic HBV infection is a major cause for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It is estimated that about 800 000–1 000 000 people die each year due to the consequences of chronic HBV infection.1 Moreover, in almost all HBV-associated HCCs integrated HBV-DNA is found. Therapy options at present are limited and based on nucleoside/nucleotide analogues and interferon alpha. Since persistence of HBV infection frequently can be attributed to an insufficient cellular immune response approaches to rescue host immune response may help to eliminate infected cells and to suppress virus replication. A recent development are HBV-specific CARs (chimeric antigen receptors) human T-cells that are intended to recognise and eliminate HBV positive…

Leggi
Marzo 2024