Respiratory Syncytial Virus Induced Type I IFN Production by pDC Is Regulated by RSV-Infected Airway Epithelial Cells, RSV-Exposed Monocytes and Virus Specific Antibodies

Schijf, Marcel A.; Lukens, Michaël V.; Kruijsen, Debby; Uden, Nathalie O. van; Garssen, Johan; Coenjaerts, Frank E. J.; Land, Belinda van‘t; Bleek, Grada M. van

doi:10.1371/journal.pone.0081695

Cited by 43 publications

(42 citation statements)

References 73 publications

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“…Therefore, mechanisms leading to IFN-α inhibition will depend on the nature of the stimuli induced both by cell surface receptors and by intracellular pathways43. IFN-α production in the presence of virus/IgG immune complexes has been previously reported with other viruses444546. For HIV-1 infection, additional studies will be necessary to define the specific Ab feature and the mechanism by which they will selectively inhibit or maintain IFN-α production by pDC.…”

Section: Discussionmentioning

confidence: 99%

Neutralizing Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production

Lederle

Holl

et al. 2014

Sci Rep

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Plasmacytoid dendritic cells (pDC) expressing FcγRIIa are antigen-presenting cells able to link innate and adaptive immunity and producing various cytokines and chemokines. Although highly restricted, they are able to replicate HIV-1. We determined the activity of anti-HIV-1 neutralizing antibodies (NAb) and non-neutralizing inhibitory antibodies (NNIAb) on the infection of primary pDC by HIV-1 primary isolates and analyzed cytokines and chemokines production. Neutralization assay was performed with primary pDC in the presence of serial antibodies (Ab) concentrations. In parallel, we measured the release of cytokines and chemokines by ELISA and CBA Flex assay. We found that NAb, but not NNIAb, inhibit HIV-1 replication in pDC. This inhibitory activity was lower than that detected for myeloid dendritic cells (mDC) infection and independent of FcγRIIa expressed on pDC. Despite the complete protection, IFN-α production was detected in the supernatant of pDC treated with NAb VRC01, 4E10, PGT121, 10-1074, 10E8, or polyclonal IgG44 but not with NAb b12. Production of MIP-1α, MIP-1β, IL-6, and TNF-α by pDC was also maintained in the presence of 4E10, b12 and VRC01. These findings suggest that pDC can be protected from HIV-1 infection by both NAb and IFN-α release triggered by the innate immune response during infection.

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Section: Discussionmentioning

confidence: 99%

Neutralizing Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production

Lederle

Holl

et al. 2014

Sci Rep

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“…Inhibition or inadequate activation of T cells resulting in lower secretion of IFN‐γ may explain this high rate of reinfections 7, 8. Monocytes and T cells are both recruited to the site of RSV infection and the role of monocytes in the pathogenesis of RSV infections has been appreciated for decades 9, 10, 11, 12, 13, 14, 15. RSV increases the expression of major histocompatibility complex (MHC) molecules on monocytes, activates CD4 + T cells and induces the production of IFN‐γ by human immune cells In vitro 15.…”

Section: Introductionmentioning

confidence: 99%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

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“…Using mouse pneumonia virus, the rodent-specific form of RSV, it was shown that TLR7 was critical for the host defense response and IFN induction during infection (Davidson et al, 2011). These results were corroborated through analysis of RSV-infected human pDCs (Schijf et al, 2013). RSV is also known to decrease IFN signaling in airway epithelial cells through degradation of STAT2 (Ramaswamy et al, 2004) and through an RSV-NS1-dependent but TLR3-independent mechanism (Xu et al, 2014b).…”

Section: Rna Nucleic Acid Sensing In Viral Immunology and Autoimmunitymentioning

confidence: 66%

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

Matz

Guzman

Goodman

2019

Nucleic Acid Sensing and Immunity - Part B

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Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe’s genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.

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Respiratory Syncytial Virus Induced Type I IFN Production by pDC Is Regulated by RSV-Infected Airway Epithelial Cells, RSV-Exposed Monocytes and Virus Specific Antibodies

Cited by 43 publications

References 73 publications

Neutralizing Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production

Neutralizing Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

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