Systemic eosinophil response induced by respiratory syncytial virus

Lindemans, Caroline A.; Kimpen, Jan L. L.; Luijk, Bart; Heidema, Jojanneke; Kanters, Deon; Ent, Cornelis K. van der; Koenderman, Leo

doi:10.1111/j.1365-2249.2006.03084.x

Cited by 40 publications

(29 citation statements)

References 37 publications

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“…These results are also consistent with observations that eosinophils from infants with lower respiratory tract RSV disease demonstrated increased expression of CD11b. 38 Although ssRNA-induced CD11b expression was significantly reduced when MyD88-deficient eosinophils were used, the response was not entirely ablated. 39 These data suggest that ssRNA may operate through another as-yet unidentified recognition receptor, perhaps located in the cytosol and similar to those activated by dsRNA.…”

Section: Discussionmentioning

confidence: 99%

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

Phipps

Lam

Mahalingam

et al. 2007

Blood

276

257

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Eosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after singlestranded RNA (ssRNA) stimulation of the TLR-7-MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice. Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV-infected wild-type mice accelerated virus clearance and inhibited the development of airways hyperreactivity. Similar responses were observed when infected recipient mice were MyD88 deficient. Eosinophils isolated from infected hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater amounts of IFN regulatory factor (IRF) - IntroductionThere are numerous studies addressing the contribution of eosinophilic leukocytes to immune mechanisms regulating allergic diseases and granulomatous and fibrotic disorders, and eosinophil recruitment in response to helminthic parasite infection has been well documented. 1 In contrast, there is only limited information on the role of eosinophils in immunity against infectious pathogens. Eosinophil recruitment was observed in response to acute severe respiratory syncytial virus (RSV) infection in human infants, 2-4 and infection of airway epithelial cells results in the expression of several eosinophil chemoattractants. 5,6 However, it is not at all clear whether eosinophils contribute to host defense or to the immunopathology observed in response to RSV infection. RSV infection is the most commonly identified cause of lower respiratory tract infections in infants, and severe disease has been associated with progression to childhood asthma, a disease state characterized by a mild to moderate eosinophilia. 7,8 In addition, exacerbations of established asthma are most frequently caused by viral infections, of which RSV has been implicated. 9 Recently, transcripts encoding Toll-like receptor (TLR)-1, TLR-4, TLR-7, TLR-9, and TLR-10, all of which coordinate innate and acquired immune responses, were shown to be expressed constitutively by eosinophils. 10 Recognition of viral nucleic acids, including double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), and dsDNA, occurs via activation of TLR-3, TLR-7, and TLR-9, respectively, and results in the production of type I IFNs and the initiation of the antiviral host response. 11-15 RSV is a negative ssRNA virus that generates dsRNA during its replication cycle. Although TLR-3 and TLR-7 both recognize viral RNA, TLR-3 uses toll-interleukin receptor domain-containing adaptorinducing IFN-␤ (TRIF) and does not require MyD88, while TLR-7 signaling is MyD88 dependent. 12 These differences in adaptor usage, along with the activation of different IFN regulatory factors (IRFs), are proposed to provi...

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Section: Discussionmentioning

confidence: 99%

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

Phipps

Lam

Mahalingam

et al. 2007

Blood

276

257

View full text Add to dashboard Cite

show abstract

“…Pathological analysis showed that the dead infants had an extended peribronchiolitis and alveolitis, with infiltration by neutrophils and a few eosinophils (15)(16)(17). This problem can be reproduced in animal models, including mice and monkeys; when FI-RSV-immunized animals were challenged with RSV, there was extensive lung infiltration by neutrophils, lymphocytes, and some eosinophils, causing severe damage (18)(19)(20)(21).…”

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confidence: 99%

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Zhou

Zhong

et al. 2016

The Journal of Immunology

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Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

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“…Despite this, we used PB eosinophils in these experiments since samples containing a sufficient amount of cells were easier to obtain and involved less discomfort for the subjects. In the first set of experiments, responsiveness to poly(I:C) was examined using expression of CD11b and secretion of IL-8 as representative indicators of activation [12, 23, 24]. R-837 (ligand for TLR7) was used as a positive control.…”

Section: Resultsmentioning

confidence: 99%

TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis

Månsson

Fransson

Adner

et al. 2009

Int Arch Allergy Immunol

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Background/Aim: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. Methods: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. Results: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-ĸB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. Conclusions: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.

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Systemic eosinophil response induced by respiratory syncytial virus

Cited by 40 publications

References 37 publications

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis

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