Severe Acute Respiratory Syndrome Coronavirus Fails To Activate Cytokine-Mediated Innate Immune Responses in Cultured Human Monocyte-Derived Dendritic Cells

Ziegler, Thedi; Matikainen, Sampsa; Rönkkö, Esa; Österlund, Pamela; Sillanpää, Maarit; Sirén, Jukka; Fagerlund, Riku; Immonen, Milla; Melén, Krister; Julkunen, Ilkka

doi:10.1128/jvi.79.21.13800-13805.2005

Cited by 79 publications

(82 citation statements)

References 32 publications

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“…by guest www.bloodjournal.org From infection. It is noteworthy that neither macrophages, cDCs, fibroblasts, nor lung epithelial cells 28 are able to mount a significant type I IFN response against SARS-CoV. The lack of a significant type I IFN response in PBMCs of SARS-CoV-infected patients 23 might be due to a partial inhibition of type I IFN signaling not only in nonlymphoid cells, 51,52 but also in pDCs.…”

Section: Discussionmentioning

confidence: 92%

“…Furthermore, IFN-␤, MxA, or ISG56 mRNA expression was found in infected pDCs ( Figure 6C). Based on this evidence and the unsuccessful efforts from previous studies to determine a cell type that produces IFN-␣ in response to SARS-CoV, [25][26][27][28] we conclude that pDCs are most likely the major source of type I IFNs in SARS-CoV infection.…”

Section: Rapid Induction Of Type I Ifns In Pdcs Following Sars-cov Inmentioning

confidence: 99%

“…Primary pDCs and cDCs were isolated from peripheral blood of healthy donors and infected with SARSCoV. As described for monocyte-derived cDCs, 28 primary cDCs from healthy donors were also not able to produce significant amounts of IFN-␣ ( Figure 6A) and did not up-regulate transcripts of IFN-␤ and IFN-stimulated genes such as ISG56 and MxA, located downstream in the type I IFN signaling pathway ( Figure 6B). In contrast and as expected from the MHV experiments, pDCs were able to produce IFN-␣ early after SARS-CoV infection ( Figure 6A).…”

Section: Rapid Induction Of Type I Ifns In Pdcs Following Sars-cov Inmentioning

confidence: 99%

“…[22][23][24] Furthermore, in vitro studies have shown that neither macrophages nor monocyte-derived DCs respond to SARS-CoV infection with significant IFN-␣ production. [25][26][27][28] Nonetheless, there is clear evidence that treatment with recombinant IFN-␤ or IFN-␣ can inhibit SARS-CoV replication in vitro, [29][30][31] and, most importantly, diminish the severity of SARS-CoV infection in vivo. 32,33 Thus, although the antiviral activity of type I IFNs in SARS-CoV infections has been clearly demonstrated, it remains to be established whether a significant production of type I IFNs can be achieved upon coronavirus infection and how this may impact on virus replication and disease.…”

mentioning

confidence: 99%

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Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon

Cervantes-Barragán

Züst

Weber³

et al. 2006

Blood

365

428

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This study demonstrates a unique and crucial role of plasmacytoid dendritic cells (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs was mediated via TLR7 ensuring a swift IFN-alpha production following encounter with this cytopathic RNA virus. Furthermore, the particular type I IFN response pattern was not restricted to the murine coronavirus, but was also found in infection with the highly cytopathic human severe acute respiratory syndrome (SARS) coronavirus. Taken together, our results suggest that rapid production of type I IFNs by pDCs is essential for the control of potentially lethal coronavirus infections.

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Section: Discussionmentioning

confidence: 92%

Section: Rapid Induction Of Type I Ifns In Pdcs Following Sars-cov Inmentioning

confidence: 99%

Section: Rapid Induction Of Type I Ifns In Pdcs Following Sars-cov Inmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon

Cervantes-Barragán

Züst

Weber³

et al. 2006

Blood

365

428

View full text Add to dashboard Cite

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“…2 These observations, in conjunction with the induction of the IFN-l1/2/3 ligands by a range of viral infections and their ability to rescue virally infected cells, 2,3 have prompted a series of studies that have further investigated the antiviral properties of these cytokines. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] However, the IFN-l ligands also induce the phosphorylation of STAT1, STAT3, STAT5 2,22 and STAT4. 23 Phosphorylation of STAT1, STAT3, STAT5 in particular, suggests more complex properties for the IFN-l ligand family; STAT3 is the signaling mechanism used by members of the IL-10 family (IL-10, IL-19, IL-20, etc.…”

Section: Introductionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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SARS‐CoV‐2 multifaceted interaction with the human host. Part II: Innate immunity response, immunopathology, and epigenetics

Beacon

Su²,

Lakowski

et al. 2020

IUBMB Life

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The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2. In response to the SARS-CoV-2 infection, the innate immune response is the first line of defense, triggering multiple signaling pathways to produce interferons, pro-inflammatory cytokines and chemokines, and initiating the adaptive immune response against the virus. Unsurprisingly, the virus has developed strategies to evade detection, which can result in delayed, excessive activation of the innate immune system. The response elicited by the host depends on multiple factors, including health status, age, and sex. An overactive innate immune response can lead to a cytokine storm, inflammation, and vascular disruption, leading to the vast array of symptoms exhibited by COVID-19 patients. What is known about the expression and epigenetic regulation of the ACE2 gene and the various players in the host response are explored in this review.

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Severe Acute Respiratory Syndrome Coronavirus Fails To Activate Cytokine-Mediated Innate Immune Responses in Cultured Human Monocyte-Derived Dendritic Cells

Cited by 79 publications

References 32 publications

Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon

Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

SARS‐CoV‐2 multifaceted interaction with the human host. Part II: Innate immunity response, immunopathology, and epigenetics

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