Respiratory syncytial virus differentially activates murine myeloid and plasmacytoid dendritic cells

Boogaard, Ivette; Oosten, Marijke van; Rijt, Leonie S. van; Muskens, Femke; Kimman, Tjeerd G.; Lambrecht, Bart N.; Buisman, Anne‐Marie

doi:10.1111/j.1365-2567.2007.02613.x

Cited by 33 publications

(35 citation statements)

References 44 publications

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“…In the present study, we have provided data indicating that murine DCs are readily infected by RSV, which promotes their maturation. However, DC maturation was observed only in response to viable RSV and not UV-inactivated RSV, which would suggest that induction of DC maturation would need viral replication (25,32). In agreement with other reports, we observed significant secretion of IL-6 and IL-10 secretion by DCs infected with RSV (25,26).…”

Section: Discussionsupporting

confidence: 92%

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Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells

González

Prado

Leiva

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

178

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Respiratory syncytial virus (RSV) infection isimmunological synapse ͉ virus evasion ͉ virulence mechanism ͉ adaptive immunity R espiratory syncytial virus (RSV) is the worldwide leading cause of infant hospitalization related to airway diseases. RSV infects Ͼ70% of children in the first year of life and by age 2, almost 100% of children have been infected at least once with this virus (1, 2). In addition, RSV reinfection is extremely frequent, suggesting that naturally acquired adaptive immunity to RSV is either inefficient or transient (2-4). It is thought that clearance of RSV would require the induction of a balanced Th1/Th2 adaptive immune response capable of inducing the production of neutralizing antibodies and IFN-␥-secreting cytotoxic CD8 ϩ T cells (CTLs) (5, 6). However, RSV-specific T cell responses generally fail to efficiently clear infection (7-9). Although functional RSV-specific memory CTLs and helper T cells can be observed in the blood and spleens of infected hosts, these cells show impaired effector function in infected lung tissues (10)(11)(12)(13)(14).Dendritic cells (DCs) are ubiquitous professional antigenpresenting cells (APCs) found in lymphoid and nonlymphoid tissues, where they locate strategically to capture antigens and present them to T cells as peptides bound to either MHC class I or II molecules (15, 16). These features render DCs as key components for the initiation and modulation of T cell immunity against pathogens, such as virus. Thus, several virulent microorganisms have developed molecular mechanisms to impair DC function and prevent clearance by adaptive immunity (17-21). RSV infection causes a significant increase in the number of mature DCs in mouse lungs (22,23) and has the capacity to infect and replicate within these cells (24-27), rendering them inefficient at inducing proliferation and IFN-␥ secretion by antigenspecific T cells (24,25). Inhibition of T cell activation by RSV has been suggested to be mediated by soluble molecules secreted by RSV-infected DCs, which reduce their capacity to induce IFN-␥ secretion by T cells (28). Although recent data indicate that RSV-induced secretion of IFN-and -␣ by human DCs can impair T cell activation (29), this phenomenon could also be observed upon T cell culture with RSV particles or cells expressing RSV antigens on their surface (30, 31). However, whether RSV-mediated inhibition applies to cognate pMHC recognition by T cells and the mechanism responsible for this inhibition remain unknown.Here, we have approached these questions by evaluating the effect of RSV infection on the capacity of murine DCs to activate T cells. We observed that DCs are efficiently infected by RSV and, although these cells mature upon infection, they are rendered unable to promote T cell activation in response to cognate-, allo-, and superantigen stimuli. Upon exposure to RSV-infected DCs, T cell proliferation and IL-2 secretion were significantly impaired, and T cells became unresponsive to subsequent stimulation with anti-CD3. Inhibition was not medi...

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Section: Discussionsupporting

confidence: 92%

“…On the contrary, UV-RSV induced no significant up-regulation of maturation markers on DCs. These data are consistent with previous reports in human and murine DCs and support the notion that RSV replication might be required for DC maturation (25,32).…”

supporting

confidence: 93%

Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells

González

Prado

Leiva

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

178

View full text Add to dashboard Cite

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“…These findings suggest that Ag processing and presentation may be occurring in the lung periphery as well as in the draining lymph node. Indeed, a recent in vitro report using bone marrow-derived cDC showed that RSV infection led to activation and increased Ag-presenting function without a change in viability (39). The rapid and sustained decrease in the number of lung cDCs we see after respiratory viral infection may represent a general response to severe infection because it has also been observed in subjects with bacterial sepsis (40).…”

Section: Discussionmentioning

confidence: 95%

Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Grayson

Ramos

Rohlfing

et al. 2007

The Journal of Immunology

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Dendritic cells are ideally suited to orchestrate the innate and adaptive immune responses to infection, but we know little about how these cells respond to infection with common respiratory viruses. Paramyxoviral infections are the most frequent cause of serious respiratory illness in childhood and are associated with an increased risk of asthma. We therefore used a high-fidelity mouse model of paramyxoviral respiratory infection triggered by Sendai virus to examine the response of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) in the lung. We found that pDCs are scarce at baseline but become the predominant population of lung dendritic cells during infection. This recruitment allows for a source of IFN-α locally at the site of infection. In contrast, cDCs rapidly differentiate into myeloid cDCs and begin to migrate from the lung to draining lymph nodes within 2 h after viral inoculation. These events cause the number of lung cDCs to decrease rapidly and remain decreased at the site of viral infection. Maturation and migration of lung cDCs depends on Ccl5 and Ccr5 signals because these events are significantly impaired in Ccl5−/− and Ccr5−/− mice. cDCs failure to migrate to draining lymph nodes in Ccl5−/− or Ccr5−/− mice is associated with impaired up-regulation of CCR7 that would normally direct this process. Our results indicate that pDCs and cDCs respond distinctly to respiratory paramyxoviral infection with patterns of movement that should serve to coordinate the innate and adaptive immune responses, respectively.

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“…In particular, several laboratories have demonstrated that type I IFNs (mainly IFN-␣ and IFN-␤) and their major producers, plasmacytoid dendritic cells (pDCs), are important in protection from RSV disease. It has been reported that RSV stimulates pDCs isolated from human peripheral blood mononuclear cells (13,14) or murine bone marrow-derived pDCs (15,16) to produce type I IFNs ex vivo. Furthermore, several publications have demonstrated that RSV infection of adult mice induces pulmonary type I IFNs in vivo (17,18) and that intranasal administration of recombinant IFN-␣ significantly reduces the lung viral load, inflammation, weight loss, and clinical illness scores of RSVinfected adult mice (19).…”

mentioning

confidence: 99%

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Cormier

Shrestha

Saravia

et al. 2014

J Virol

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Respiratory syncytial virus (RSV) infection is the number one cause of bronchiolitis in infants IMPORTANCE Respiratory syncytial virus (RSV) is the most significant cause of lower respiratory tract infection in infancy worldwide.Despite the dire need, we have failed to produce efficacious RSV vaccines or therapeutics. Part of the reason for this failure is our lack of understanding of how RSV interacts with the infant immune system to suppress the development of protective immunity. In the study described in the present paper, we used a neonatal mouse model, which more closely mimics human infants, to study the role of the innate immune system, particularly type I interferons (IFNs) and plasmacytoid dendritic cells (pDCs), in the pathogenesis of RSV infection. RSV infection in neonates induced limited type I IFN and pDC responses. IFN-␣ treatment or adoptive transfer of adult pDCs capable of producing IFN-␣ prior to neonatal RSV infection decreased Th2-biased immunopathogenesis during reinfection. These data suggest that IFN-␣ is a promising target for future RSV vaccine design.

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Respiratory syncytial virus differentially activates murine myeloid and plasmacytoid dendritic cells

Cited by 33 publications

References 44 publications

Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells

Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells

Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

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