Macrophages and Dendritic Cells Are Not the Major Source of Pro-Inflammatory Cytokines Upon SARS-CoV-2 Infection

Niles, Marc A.; Gogesch, Patricia; Kronhart, Stefanie; Iannazzo, Samira Ortega; Kochs, Georg; Waibler, Zoe; Anzaghe, Martina

doi:10.3389/fimmu.2021.647824

Cited by 46 publications

(61 citation statements)

References 52 publications

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“…Arguably, ex vivo cultures of primary macrophages, albeit valuable, have a limited lifespan which can affect cell polarization and transcriptional responses after extended periods of culture. Nevertheless, our findings are aligned with reports that macrophages are unlikely to drive the initial wave of pro-inflammatory cytokines upon SARS-CoV-2 infection [29,31]. In addition, the substantial increase in induction of proinflammatory cytokines upon IFNstimulation suggests that macrophages may participate in secondary or ensuing waves of inflammatory responses leading to ARDS in severe COVID-19 patients.…”

Section: Discussionsupporting

confidence: 90%

“…In contrast Caco-2, Vero E6 and Calu-3 cell lines produced high viral loads (4 × 10 5 -5.5 × 10 5 TCID 50 / mL ) (Figure 1A). Together these findings indicate that macrophages do not support SARS-CoV-2 replication in line with other reports [28][29][30][31]. In contrast, the influenza M gene was detected in cell lysates at 6 hpi, more so in 6:2 Eng/09 infected macrophages (Figure S2).…”

Section: Macrophages Are Refractory To Sars-cov-2 Infectionsupporting

confidence: 90%

“…Earlier reports suggested that alveolar macrophages are infected by SARS-CoV-2 [24][25][26] and that the diverse expression of ACE2 on macrophages among individuals might govern the severity of SARS-CoV-2 infection [27]. Since then, several studies have demonstrated that macrophages are not permissive to SARS-CoV-2 infection [28][29][30][31]. Conversely, some reports argue that macrophages orchestrate the cytokine storm [21,24,25,30,32] while others propose that macrophages play a secondary role in the virus-associated inflammation [29,31].…”

Section: Introductionmentioning

confidence: 99%

“…Since then, several studies have demonstrated that macrophages are not permissive to SARS-CoV-2 infection [28][29][30][31]. Conversely, some reports argue that macrophages orchestrate the cytokine storm [21,24,25,30,32] while others propose that macrophages play a secondary role in the virus-associated inflammation [29,31].…”

Section: Introductionmentioning

confidence: 99%

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Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection

Zhang

Penn

Barclay

et al. 2022

Viruses

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Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain. Virus replication was monitored by qRT-PCR for the E viral gene for SARS-CoV-2 or M gene for influenza and TCID50 or plaque assay, and cytokine levels were assessed semiquantitatively with qRT-PCR and a proteome cytokine array. We report that MDM are not susceptible to SARS-CoV-2 whereas both influenza viruses replicated in MDM, albeit abortively. We observed a modest cytokine response in SARS-CoV-2 exposed MDM with notable absence of IFN-β induction, which was instead strongly induced by the influenza viruses. Pre-treatment of MDM with IFN-α enhanced proinflammatory cytokine expression upon exposure to virus. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages.

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Section: Discussionsupporting

confidence: 90%

Section: Macrophages Are Refractory To Sars-cov-2 Infectionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection

Zhang

Penn

Barclay

et al. 2022

Viruses

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“…Moreover, the relative number of CD14++ CD16+ monocytes comprised up to 45% of all monocytes. By comparison, other studies by Niles et al [19] showed that myeloid dendritic cells (mDCs), and neither M1 pro-inflammatory macrophages nor M2 anti-inflammatory macrophages, were stimulated to produce pro-inflammatory cytokines in SARS-COV-2 infection. Many differences have also been described between the severe course of COVID-19 and typical MAS.…”

Section: Introductionmentioning

confidence: 77%

Interplay between Neutrophils, NETs and T-Cells in SARS-CoV-2 Infection—A Missing Piece of the Puzzle in the COVID-19 Pathogenesis?

Niedźwiedzka-Rystwej

Grywalska

Hrynkiewicz

et al. 2021

Cells

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Since the end of 2019, a new, dangerous virus has caused the deaths of more than 3 million people. Efforts to fight the disease remain multifaceted and include prophylactic strategies (vaccines), the development of antiviral drugs targeting replication, and the mitigation of the damage associated with exacerbated immune responses (e.g., interleukin-6-receptor inhibitors). However, numerous uncertainties remain, making it difficult to lower the mortality rate, especially among critically ill patients. While looking for a new means of understanding the pathomechanisms of the disease, we asked a question—is our immunity key to resolving these uncertainties? In this review, we attempt to answer this question, and summarize, interpret, and discuss the available knowledge concerning the interplay between neutrophils, neutrophil extracellular traps (NETs), and T-cells in COVID-19. These are considered to be the first line of defense against pathogens and, thus, we chose to emphasize their role in SARS-CoV-2 infection. Although immunologic alterations are the subject of constant research, they are poorly understood and often underestimated. This review provides background information for the expansion of research on the novel, immunity-oriented approach to diagnostic and treatment possibilities.

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The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

Sviercz,

Jarmoluk,

Godoy Coto

et al. 2024

Journal of Medical Virology

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The Coronavirus Disease 2019 (COVID‐19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the respiratory system, the impact of COVID‐19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS‐CoV‐2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte‐derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS‐CoV‐2 strains heightened osteoclast formation in a dose‐dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS‐CoV‐2 induced early pro‐inflammatory M1 macrophage polarization, shifting toward an M2‐like profile. Osteoclastogenesis‐related genes (RANK, NFATc1, DC‐STAMP, MMP9) were upregulated, and surprisingly, SARS‐CoV‐2 variants promoted RANKL‐independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS‐CoV‐2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID‐19.

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Macrophages and Dendritic Cells Are Not the Major Source of Pro-Inflammatory Cytokines Upon SARS-CoV-2 Infection

Cited by 46 publications

References 52 publications

Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection

Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection

Interplay between Neutrophils, NETs and T-Cells in SARS-CoV-2 Infection—A Missing Piece of the Puzzle in the COVID-19 Pathogenesis?

The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

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