Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

Lv, Jiadi; Wang, Zhenfeng; Qu, Yajin; Zhu, Hua; Zhu, Quan; Tong, Wei; Bao, Linlin; Lv, Qi; Cong, Jason; Li, Dan; Deng, Wei; Yü, Ping; Song, Jiangping; Liu, Jiangning; Liu, Yuying; Qin, Chuan; Huang, Bo

doi:10.1038/s41421-021-00258-1

Cited by 96 publications

(113 citation statements)

References 47 publications

(36 reference statements)

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“…Single-cell RNA analysis of BALF showed depletion of alveolar macrophages in COVID-19. These cells were shown to be infected by SARS-CoV-2 in vitro and in autopsy samples, although their expression of the virus entry receptor angiotensin-converting enzyme 2 (ACE2) and the mechanism of viral entry are unclear 92 – 96 . As alveolar macrophages activate inflammasomes during acute lung injury in mice, it will be important to determine whether this also occurs after SARS-CoV-2 infection through direct or indirect mechanisms.…”

Section: Demonstration Of Inflammasome Activationmentioning

confidence: 99%

Inflammasome activation at the crux of severe COVID-19

2021

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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), results in life-threatening disease in a minority of patients, especially elderly people and those with co-morbidities such as obesity and diabetes. Severe disease is characterized by dysregulated cytokine release, pneumonia and acute lung injury, which can rapidly progress to acute respiratory distress syndrome, disseminated intravascular coagulation, multisystem failure and death. However, a mechanistic understanding of COVID-19 progression remains unclear. Here we review evidence that SARS-CoV-2 directly or indirectly activates inflammasomes, which are large multiprotein assemblies that are broadly responsive to pathogen-associated and stress-associated cellular insults, leading to secretion of the pleiotropic IL-1 family cytokines (IL-1β and IL-18), and pyroptosis, an inflammatory form of cell death. We further discuss potential mechanisms of inflammasome activation and clinical efforts currently under way to suppress inflammation to prevent or ameliorate severe COVID-19.

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Section: Demonstration Of Inflammasome Activationmentioning

confidence: 99%

Inflammasome activation at the crux of severe COVID-19

2021

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“…Accordingly, investigation of cell tropism and immune activation profiles of SARS-CoV-2 in ex vivo organ cultures of human lung tissues revealed infection of type I and II pneumocytes as well as AMs ( 124 ), confirmed by detection of SARS-CoV-2 in AMs in autopsy samples from COVID-19 patients ( 125 ). Interestingly, analysis of murine AMs derived from human (h)ACE2 transgenic animals revealed different susceptibility to SARS-CoV-2 infection depending on their cytokine-induced polarization as in vitro treatment with IFN-γ and LPS caused increased infection rates compared to pre-treatment with IL-4 ( 126 ). Furthermore, in vitro treatment of PMA-differentiated THP-1 human macrophages and isolated CD14 + monocytes with SARS-CoV-2 spike protein after LPS stimulation exposed a hyperresponsiveness to TLR signals by suppression of IRAK-M ( 127 ).…”

Section: The Role Of Monocytes and Alveolar Macrophages In Covid-19mentioning

confidence: 99%

Monocytes and Macrophages in COVID-19

2021

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COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The disease is characterized primarily, but not exclusively, by respiratory clinical manifestations ranging from mild common cold symptoms, including cough and fever, to severe respiratory distress and multi-organ failure. Macrophages, a heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes of complex ontogeny present in all mammalian organs, play critical roles in developmental, homeostatic and host defense processes with tissue-dependent plasticity. In case of infection, they are responsible for early pathogen recognition, initiation and resolution of inflammation, as well as repair of tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, are recruited under pathological conditions such as viral infections to the affected tissue to defend the organism against invading pathogens and to aid in efficient resolution of inflammation. Given their pivotal function in host defense and the potential danger posed by their dysregulated hyperinflammation, understanding monocyte and macrophage phenotypes in COVID-19 is key for tackling the disease’s pathological mechanisms. Here, we outline current knowledge on monocytes and macrophages in homeostasis and viral infections and summarize concepts and key findings on their role in COVID-19. While monocytes in the blood of patients with moderate COVID-19 present with an inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized by loss of HLA-DR expression and induction of S100 alarmin expression is their dominant feature in severe disease. Pulmonary macrophages in COVID-19 derived from infiltrating inflammatory monocytes are in a hyperactivated state resulting in a detrimental loop of pro-inflammatory cytokine release and recruitment of cytotoxic effector cells thereby exacerbating tissue damage at the site of infection.

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“…However, viral particles are rarely detected in blood samples from infected patients [64][65][66], suggesting that viremia is not the primary mechanism for viral spreading through the body. An alternative diffusion route may be represented by replication into the reticularendothelial system, as alveolar macrophage seems able to uptake, amplificate and then release the virus [67].…”

Section: Ace2 and Organ Tropism Of Sars-cov2mentioning

confidence: 99%

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

Zanza

Tassi

Romenskaya

et al. 2021

Cells

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Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.

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Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

Cited by 96 publications

References 47 publications

Inflammasome activation at the crux of severe COVID-19

Inflammasome activation at the crux of severe COVID-19

Monocytes and Macrophages in COVID-19

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

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