The Lung Microvasculature Is a Functional Immune Niche

Granton, Elise; Kim, Junghwan; Podstawka, John; Yipp, Bryan G.

doi:10.1016/j.it.2018.09.002

Cited by 29 publications

(33 citation statements)

References 57 publications

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“…Previously extravasated neutrophils may also re-enter circulation, migrate to the pulmonary microcirculation where they upregulate CXCR4 to subsequently enter the BM for clearance ( 20 ). Further, the lung microvasculature has been recognized as a functional immune niche ( 21 , 22 ). Of note, most studies investigating the differentiation processes have been performed in mouse models and might thus not be fully translatable to human neutrophils ( 23 ).…”

Section: Neutrophil Ontologymentioning

confidence: 99%

Neutrophils in COVID-19

et al. 2021

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Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-19.

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Section: Neutrophil Ontologymentioning

confidence: 99%

Neutrophils in COVID-19

et al. 2021

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“…Several groups have hypothesized that neutrophil margination acts as a protective mechanism to de-prime and sequester activated neutrophils, thus preventing further damage [46][47][48]. Recently, supported by the observation that marginated lung neutrophils express the major histocompatibility complex II and interact with B cells in the lung microvasculature [49], Granton et al hypothesized that the lung-as with the spleen and liver-may act as an immunological niche [50]. While both theories may support physiological roles to maintain homeostasis and control the immune response, more studies will be needed to elucidate the role for neutrophil margination in the lung microvasculature at steady-state and upon stress responses ( Figure 1).…”

Section: Homeostasismentioning

confidence: 99%

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

Giacalone

Margaroli

Mall

et al. 2020

IJMS

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Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

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“…An IL-1b/NET/coagulation pathway has been invoked in thrombogenesis in a cohort of acute coronary syndrome patients with high circulating CRP (Liberale et al, 2019). The lungs are particularly susceptible to immunothrombosis, given the readily available pool of neutrophils (Granton et al, 2018) and platelets (Lefrancais et al, 2017). In this scenario, a viral-induced inflammation promotes the formation of NETs by activated neutrophils.…”

Section: Lung-centric Immunothrombosismentioning

confidence: 99%

COVID-19: Lung-Centric Immunothrombosis

Kvietys

Kadan

Yaqinuddin

et al. 2021

Front. Cell. Infect. Microbiol.

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The respiratory tract is the major site of infection by SARS-CoV-2, the virus causing COVID-19. The pulmonary infection can lead to acute respiratory distress syndrome (ARDS) and ultimately, death. An excessive innate immune response plays a major role in the development of ARDS in COVID-19 patients. In this scenario, activation of lung epithelia and resident macrophages by the virus results in local cytokine production and recruitment of neutrophils. Activated neutrophils extrude a web of DNA-based cytoplasmic material containing antimicrobials referred to as neutrophil extracellular traps (NETs). While NETs are a defensive strategy against invading microbes, they can also serve as a nidus for accumulation of activated platelets and coagulation factors, forming thrombi. This immunothrombosis can result in occlusion of blood vessels leading to ischemic damage. Herein we address evidence in favor of a lung-centric immunothrombosis and suggest a lung-centric therapeutic approach to the ARDS of COVID-19.

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The Lung Microvasculature Is a Functional Immune Niche

Cited by 29 publications

References 57 publications

Neutrophils in COVID-19

Neutrophils in COVID-19

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

COVID-19: Lung-Centric Immunothrombosis

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