About this Research Topic
Cytokines are a broad group of soluble proteins secreted during pathogen infection by infected and non-infected immune cells with both pro-inflammatory and anti-inflammatory effector functions that stimulate or inhibit systematic inflammation. Inflammation coordinates the first line of host defenses that activate both innate and adaptive immune responses against infectious diseases. While many cytokines have beneficial effects facilitating pathogen clearance or promoting tissue repair, other cytokines exert serious harm to the host, inflicting tissue damage that leads to disease through an immunopathogenic process known as 'cytokine storm'. The term 'cytokine storm' was first described in the early 1990s as a complication of allogenic tissue graft transplantation, or graft-versus-host disease (GVHD), whereby donor T cells produce excessive quantities of proinflammatory cytokines that induce damage and pathology on the naïve recipient tissues.
In the last decades, the phenomenon of cytokine storm has been adopted to describe the aberrant, unbalanced release of pro-inflammatory and/or vasoactive mediators and the accompanying immunopathology that ensues during viral, bacterial, and fungal infections. Today, cytokine storms have been reported in many severe viral and bacterial infections, particularly sepsis, one of the main results from complicated interactions between the infecting pathogen and the host immune system which accounts for abrupt outbreaks every year, including millions of infections and deaths worldwide.
Pathogens causing systemic inflammatory response syndrome associated to cytokine storms include bacterial infections, such as those caused by Staphylococcus aureus, Haemophilus influenzae, and Francisella tularensis, and viruses including influenza viruses, coronaviruses, flavivirus, as well as other clinically important infectious diseases caused by Rickettsia spp., arenaviruses, bunyaviruses, rotavirus, and lentiviruses such as HIV, among others. In these pathogen infections, the acute inflammatory response is significantly marked by the presence of elevated levels of cytokines and chemokines and the recruitment of inflammatory cells that trigger an inflammatory cascade accompanied by abundant tissue damage. This cascade of events has been repeatedly associated with poor prognosis of clinical outcomes and pathogenesis in humans and animal models, mainly related to overwhelming systemic inflammation, hemodynamic instability, and multiple organ dysfunction, sometimes resulting in death.
Despite clinical evidence and extensive basic research and clinical studies, the pathophysiology of cytokine storms remains poorly understood. Increasing evidence clearly suggests that this phenomenon is heterogeneous and dynamic and does not belong to a single group of pathogens, as it has been associated with a wide variety of infectious and non-infectious diseases with varying clinical outcomes despite therapeutic intervention.
This Research Topic will focus on better understanding the role of cytokine storms in promoting immunopathology during bacterial and viral infections.
We welcome articles which address the following:
• emerging advances in infections caused by these pathogens and cytokine storms;
• molecular mechanisms and host and viral factors underlying uncontrolled cytokine responses upon viral infection;
• targets for next-generation diagnostic tools;
• novel therapeutic interventions, and vaccine development.
Keywords: Cytokine storm, inflammation, pathogenesis, bacteria, viruses, severe disease, therapeutics & vaccine targets
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