Negar Karimi

Mast cells (MCs) are abundant at sites exposed to the external environment and pathogens. Local activation of these cells, either directly via pathogen recognition or indirectly via interaction with other activated immune cells and results in the release of pre-stored mediators in MC granules. The release of these pre-stored mediators helps to enhance pathogen clearance. While MCs are well known for their protective role against parasites, there is also significant evidence in the literature demonstrating their ability to respond to viral, bacterial, and fungal infections. Vitamin D is a fat-soluble vitamin and hormone that plays a vital role in regulating calcium and phosphorus metabolism to maintain skeletal homeostasis. Emerging evidence suggests that vitamin D also has immunomodulatory properties on both the innate and adaptive immune systems, making it a critical regulator of immune homeostasis. Vitamin D binds to its receptor, called the vitamin D receptor (VDR), which is present in almost all immune system cells. The literature suggests that a vitamin D deficiency can activate MCs, and vitamin D is necessary for MC stabilization. This manuscript explores the potential of vitamin D to regulate MC activity and combat pathogens, with a focus on its ability to fight viruses.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in OA pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating certain protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with OA, and possible therapeutic approaches to target neutrophils for the treatment of OA are described. Since neutrophils play a complex role in the pathophysiology of osteoarthritis, contributing to joint degradation as well as joint repair, targeting these cells is likely to pave the way for a potential therapeutic approach for the management of OA. Future studies are needed to investigate the use of targeted therapies to modulate neutrophil function and identify their subpopulations that are associated with osteoarthritis progression or response to treatment.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although the complexity of the heterogeneity of neutrophils is still in the process of being uncovered, evidence indicates that they display phenotypes and functions that can assist in viral clearance or augment and amplify the immunopathology of viruses. Therefore, deciphering and understanding neutrophil subsets and their polarization in viral infections is of importance. In this review, the different phenotypes of neutrophils and the roles they play in viral infections are discussed. We also examine the possible ways to target neutrophil subsets during viral infections as potential anti-viral treatments.

Mast cells (MCs) are heterogenous innate leukocytes producing many inflammatory mediators during viral infections that can be protective or damaging to the host, as is seen in the infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease that was first identified in 2019 (COVID-19). MCs can sense viruses by diverse mechanisms. They express angiotensin-converting enzyme 2 (ACE2), known as the principal entry receptor for SARS-CoV-2, and tryptase that can promote SARS-CoV-2 infection. Tryptase is one of the most abundant serine proteases released by MCs during degranulation and is reported to have both beneficial and detrimental roles in respiratory diseases. Reviewed here are the potential roles of MC-derived tryptase during COVID-19, the implications it has in the pathogenesis of SARS-CoV-2, and the possibility of treating COVID-19 by targeting tryptase.

A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.

Influenza viruses have affected the world for over a century, causing multiple pandemics. Throughout the years, many prophylactic vaccines have been developed for influenza; however, these viruses are still a global issue and take many lives. In this paper, we review influenza viruses, associated immunological mechanisms, current influenza vaccine platforms, and influenza infection, in the context of immunocompromised populations. This review focuses on the qualitative nature of immune responses against influenza viruses, with an emphasis on trained immunity and an assessment of the characteristics of the host–pathogen that compromise the effectiveness of immunization. We also highlight innovative immunological concepts that are important considerations for the development of the next generation of vaccines against influenza viruses.

Cytokine storm syndrome is a cascade of escalated immune responses disposing the immune system to exhaustion, which might ultimately result in organ failure and fatal respiratory distress. Infection with severe acute respiratory syndrome-coronavirus-2 can result in uncontrolled production of cytokines and eventually the development of cytokine storm syndrome. Mast cells may react to viruses in collaboration with other cells and lung autopsy findings from patients that died from the coronavirus disease that emerged in 2019 (COVID-19) showed accumulation of mast cells in the lungs that was thought to be the cause of pulmonary edema, inflammation, and thrombosis. In this review, we present evidence that a cytokine response by mast cells may initiate inappropriate antiviral immune responses and cause the development of cytokine storm syndrome. We also explore the potential of mast cell activators as adjuvants for COVID-19 vaccines and discuss the medications that target the functions of mast cells and could be of value in the treatment of COVID-19. Recognition of the cytokine storm is crucial for proper treatment of patients and preventing the release of mast cell mediators, as impeding the impacts imposed by these mediators could reduce the severity of COVID-19.