RNA Sensors Enable Human Mast Cell Anti-Viral Chemokine Production and IFN-Mediated Protection in Response to Antibody-Enhanced Dengue Virus Infection

Brown, Michael G.; McAlpine, Sarah M.; Huang, Yan; Haidl, Ian D.; Al-Afif, Ayham; Marshall, Jean S.; Anderson, Robert

doi:10.1371/journal.pone.0034055

Cited by 65 publications

(77 citation statements)

References 54 publications

(72 reference statements)

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“…In contrast, the expression of TNF‐α and IL‐6 was decreased significantly on days 3 and 5 pi in SCG‐treated mice, which suggests that SCG could improve the mortality of virus‐infected mice by preventing the overproduction of proinflammatory cytokines. Many studies have found that mast cells could be involved in virus infection using TLR3, RIG‐I, and MDA5 to sense viral RNA 43, 44, 45. In our study, the expression of TLR3 and TRIF in the lungs of SCG‐treated mice decreased, which suggested that SCG might have some roles in the TLR3 pathway in mast cells during H5N1 infection.…”

Section: Discussionsupporting

confidence: 49%

The therapeutic effects of sodium cromoglycate against influenza A virus H5N1 in mice

Han

Wei

Zhang

et al. 2015

Influenza Resp Viruses

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ObjectivesTo identify the protective role of sodium cromoglycate in mice during influenza virus infection.DesignH5N1 virus‐infected mice were treated with the mast cell stabilizer sodium cromoglycate (SCG) to investigate its therapeutic effect.SampleThe nose, trachea and lungs from mice were collected.Main outcome measuresVirus replication and host responses were determined by plaque assay, quantitative PCR, immunohistochemistry, and histology.ResultsSCG‐treated mice survived better than did PBS‐treated mice after H5N1 virus infection. Mild pathological changes with fewer inflammatory cell infiltration and fewer virus antigens were observed in the nose, trachea, and lungs of SCG‐treated mice on days 3 and 5 post‐infection. However, no significant changes in viral load in the lungs were detected between SCG‐ and PBS‐treated mice. Furthermore, significantly decreased expression of interleukin‐6, tumor necrosis factor‐a, Toll‐like receptor 3, and TIR‐domain‐containing adapter‐inducing interferon‐b was detected in the lungs of SCG‐treated mice, and no higher expression of interferon‐c was detected.ConclusionThese results suggest that SCG has therapeutic roles in H5N1 virus‐infected mice by alleviating the inflammatory response rather than inhibition of viral replication in the lungs.

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Section: Discussionsupporting

confidence: 49%

The therapeutic effects of sodium cromoglycate against influenza A virus H5N1 in mice

Han

Wei

Zhang

et al. 2015

Influenza Resp Viruses

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“…However, specific chemokines, such as CCL4 (MIP-1b), CCL5 (RANTES) and CXCL10 (IP-10) released from mast cells could also contribute to the recruitment of T cells and NK cells, both of which are important for suppressing viral infection. [16][17][18] Mast cells also contribute to immune surveillance, responding to DENV by activating host antiviral responses and releasing chemokines CX3CL1 (Fractalkine), CXCL12 (SDF-1) and CCL5 (RANTES) that recruit additional immune cells. 17,18 Mast cells produce TNF-a, which activates endothelial cells 15 as well as chymase which can increase vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

“…RIG-I and MDA5). 16,18,19 The activated mast cells also produce chemokines, which recruit NK, NKT and T cells and then help to clear the virus. However, if local control mechanisms fail, the virus will enter the blood and be carried to other organs.…”

Section: Discussionmentioning

confidence: 99%

“…15 Mast cells infected with several viruses including DENV produce a spectrum of chemokines that recruit specific leucocytes including natural killer (NK) cells. [16][17][18] In a mouse model of DENV infection, mast cells were implicated in recruitment of NK and NKT cells, which may clear virus. 18 RNA sensors, particularly RIG-I, enable human mast cell antiviral chemokine production and interferon-mediated protection in response to antibody-enhanced DENV infection.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…18 RNA sensors, particularly RIG-I, enable human mast cell antiviral chemokine production and interferon-mediated protection in response to antibody-enhanced DENV infection. 16 Localized responses of mast cells to DENV are protective through immune cell recruitment and viral clearance, whereas mast cell-induced vascular leakage systemically can contribute to DENV pathogenesis. 19 Mast cell-deficient Kit W-sh/W-sh mice are often used as a model to study the function of mast cells in human disease.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

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Mast cell–macrophage dynamics in modulation of dengue virus infection in skin

et al. 2015

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SummaryDengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient Kit W-sh/W-sh mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two-to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected Kit W-sh/W-sh mice than in DENV-infected wild-type (WT) mice (using a dose of 1 3 10 9 plaqueforming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected Kit W-sh/W-sh mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from Kit W-sh/W-sh and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from Kit W-sh/W-sh mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated Kit W-sh/W-sh mice than in corresponding WT mice. In summary, compared with WT mice, Kit W-sh/W-sh mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.

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Interferon α2 and interferon γ induce the degranulation independent production of VEGF‐A and IL‐1 receptor antagonist and other mediators from human mast cells

Oldford

Salsman

Portales‐Cervantes

et al. 2017

Immunity Inflam & Disease

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BackgroundMast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma.ObjectiveTo define the selective human mast cell cytokine and chemokine response following activation with type I or type II IFN's.MethodsThe ability of both IFNα2 and IFNγ to induce cytokine production by human cord blood‐derived mast cells was examined in vitro. Cytokine and chemokine production at 6 and 24 h was assessed by multiplex protein analysis. Degranulation was assessed by β‐hexosaminidase release. Mast cells were also treated with reovirus or respiratory syncytial virus and their production of CXCL10, IL‐1 receptor antagonist (IL‐1Ra), and vascular endothelial growth factor (VEGF) examined after 24 h.ResultsIn addition to increased expression of classical IFN response genes, such as CXCL10, small but significant increases in CCL5 and IL‐17 production were observed following IFN activation. Notably, human mast cells produced both VEGF and IL‐1Ra in a dose dependent manner. These responses occurred in the absence of mast cell degranulation by a mechanism consistent with classical IFN signaling. Both reovirus and respiratory syncytial virus infection of mast cells, were also associated with IFN‐dependent IL‐1Ra expression.Conclusion and Clinical RelevanceOur findings demonstrate that IFNs have profound impact on cytokine and chemokine expression by human mast cells, alone or in the context of viral infection. Mast cell VEGF and IL‐1Ra responses to IFNs could impact the regulation of local inflammatory responses and subsequent tissue remodeling.

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RNA Sensors Enable Human Mast Cell Anti-Viral Chemokine Production and IFN-Mediated Protection in Response to Antibody-Enhanced Dengue Virus Infection

Cited by 65 publications

References 54 publications

The therapeutic effects of sodium cromoglycate against influenza A virus H5N1 in mice

The therapeutic effects of sodium cromoglycate against influenza A virus H5N1 in mice

Mast cell–macrophage dynamics in modulation of dengue virus infection in skin

Interferon α2 and interferon γ induce the degranulation independent production of VEGF‐A and IL‐1 receptor antagonist and other mediators from human mast cells

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