Background. Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the ...relevance of PEM as a risk factor for influenza. Methods. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. Results. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8⁺ T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Conclusions. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.
Microvascular injury immediately following reperfusion therapy in acute myocardial infarction (MI) has emerged as a driving force behind major adverse cardiovascular events in the postinfarction ...period. Although postmortem investigations and animal models have aided in developing early understanding of microvascular injury following reperfusion, imaging, particularly serial noninvasive imaging, has played a central role in cultivating critical knowledge of progressive damage to the myocardium from the onset of microvascular injury to months and years after in acute MI patients. This review summarizes the pathophysiological features of microvascular injury and downstream consequences, and the contributions noninvasive imaging has imparted in the development of this understanding. It also highlights the interventional trials that aim to mitigate the adverse consequences of microvascular injury based on imaging, identifies potential future directions of investigations to enable improved detection of disease, and demonstrates how imaging stands to play a major role in the development of novel therapies for improved management of acute MI patients.
In a clinical bulletin published by American College of Cardiology in February 2020, it was revealed that the case fatality rate of coronavirus disease 2019 (COVID-19) pandemic for patients with ...cardiovascular disease is 10.5%. Heart failure (HF) is a global pandemic affecting at least 26 million people worldwide and is increasing in prevalence. Looking at the historical prospectus of practice of clinical cardiology in most countries, patients with left ventricular ejection fraction (LVEF) < 40% presented periodically to exhibit worsening signs and symptoms. The superimposition of novel respiratory tract pathogens like COVID-19 can have accelerated inflammatory injury. Immunosenescense, overactive immune response or direct viral toxicity are hypothetical mechanisms of cardiac injury. Undoubtedly, all countries have to proactively approach their cardiovascular disease (CVD) patient population due to high vulnerability from individual and epidemiological risk factors.
Microvascular injury immediately following reperfusion therapy in acute myocardial infarction (MI) has emerged as a driving force behind major adverse cardiovascular events in the postinfarction ...period. Although postmortem investigations and animal models have aided in developing early understanding of microvascular injury following reperfusion, imaging, particularly serial noninvasive imaging, has played a central role in cultivating critical knowledge of progressive damage to the myocardium from the onset of microvascular injury to months and years after in acute MI patients. This review summarizes the pathophysiological features of microvascular injury and downstream consequences, and the contributions noninvasive imaging has imparted in the development of this understanding. It also highlights the interventional trials that aim to mitigate the adverse consequences of microvascular injury based on imaging, identifies potential future directions of investigations to enable improved detection of disease, and demonstrates how imaging stands to play a major role in the development of novel therapies for improved management of acute MI patients.
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•In patients reperfused for acute MI, microvascular injury following reperfusion therapy substantially increases the risk for MACE, with those that develop intramyocardial hemorrhage within the MI zone carrying the greatest risk for MACE in the post-MI period.•Currently available advanced imaging techniques can noninvasively detect and accurately characterize the type of microvascular injury following reperfusion therapy as those with microvascular obstruction only or microvascular obstruction and intramyocardial hemorrhage.•Therapies to mitigate reperfusion injury and improve outcomes need to take the type and extent of microvascular injury into account.
To better understand the early virus-host interactions of the pandemic 2009 A(H1N1) viruses in humans, we examined early host responses following infection of human epithelial cell cultures with ...three 2009 A(H1N1) viruses (A/California/08/2009, A/Mexico/4108/2009, and A/Texas/15/2009), or a seasonal H1N1 vaccine strain (A/Solomon Islands/3/2006). We report here that infection with pandemic A/California/08/2009 and A/Mexico/4108/2009 viruses resulted in differences in virus infectivity compared to either pandemic A/Texas/15/2009 or the seasonal H1N1 vaccine strain. In addition, IFN-β levels were decreased in cell cultures infected with either the A/California/08/2009 or the A/Mexico/4108/2009 virus. Furthermore, infection with A/California/08/2009 and A/Mexico/4108/2009 viruses resulted in lower expression of four key proinflammatory markers (IL-6, RANTES, IP-10, and MIP-1β) compared with infection with either A/Texas/15/2009 or A/Solomon Islands/3/2006. Taken together, our results demonstrate that 2009 A(H1N1) viruses isolated during the Spring wave induced varying degrees of early host antiviral and inflammatory responses in human respiratory epithelial cells, highlighting the strain-specific nature of these responses, which play a role in clinical disease.
Abstract
Activation of innate immunity pathways in susceptible cell types is critical for host defense against influenza-A viruses (IAV). Based on studies signifying a role for NOX1 in inflammation, ...we hypothesized that IAV of seasonal and pandemic potential may induce different isoforms of NOX enzymes in the respiratory tract, and that attenuation of virus strain-specific NOX enzymes can be exploited to prevent and/or treat severity of disease. Using three respiratory tract-relevant cell lines (epithelial/A549, endothelial/HULEC, and monoctytic/THP1) and three strains of IAV (H1N1/PR8, H3N2/X31, H1N1/WSN), we found significant upregulation of NOX1 in all three cell lines (e.g.-A549: PR8/55 fold; X31/35 fold; WSN/12,250 fold). Furthermore, in contrast to the epithelial cell line showing NOX1 expression by 4h with peak levels at 16h, the monocytic cell line showed delayed (8h) and sustained (48h) levels of NOX1. Interestingly, inhibition of NOX-isoforms in IAV-infected epithelial cells by diphenyleneiodonium (DPI), at a concentration (25μM), which did not impact cell death, showed significant decrease (75%) in virus triggered NOX1 levels. In addition, NOX-inhibition led to significant decrease in virus-induced chemokines (MCP1, MIP3, MIP1β, RANTES, and IP10) and proinflammatory cytokines (IL1α, IL6, IL8, and TNFα). Furthermore, decline in NOX1 correlated with a modest increase in viral NS1. Taken together, in addition to showing definitive evidence for upregulation of NOX1 in response to subtypes of IAV, our results strongly support a role for NOX1 in IAV-driven inflammation.
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