Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease

Malinczak, Carrie‐Anne; Fonseca, Wendy; Rasky, Andrew J.; Ptaschinski, Catherine; Morris, Susan H.; Ziegler, Steven F.; Lukacs, Nicholas W.

doi:10.1038/s41385-019-0171-3

Cited by 71 publications

(78 citation statements)

References 73 publications

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“…This result is similar to a prevalence study in Brazil [20]. Nevertheless, some studies in the literature have revealed male as a risk factor to acquire RSV infection, but this observation is currently not well de ned [19,20,21].…”

Section: Discussionsupporting

confidence: 89%

Seroepidemiology of Respiratory Syncytial Virus infection in rural and semi-rural areas of the Littoral Region of Cameroon

Mandi

Yimer²,

Bekolo

et al. 2020

Preprint

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Background: The respiratory syncytial virus (RSV) has been established as a leading cause of acute lower respiratory illness (ALRI) in infants and children. In 2015, the global disease burden (GBD) study estimated that the overall RSV-ALRI mortality could be as high as 118200, with most death occurring in low- and middle-incomes countries (LMICs). This study aimed to assess the burden of RSV infection among children less than two years with acute respiratory infections (ARI) in the littoral region of Cameroon.Methods: We carried out a cross-sectional study in seven health in the littoral region of Cameroon. Venous blood was collected using serum separation tubes from eligible children who visited these healthcare facilities with acute respiratory infections. ELISA testing was used to assess the seroprevalence of anti-IgM RSV for the total population and by selected demographic and health parameters and potential risk factors. Results: The overall RSV-associated ARI seroprevalence was 33% (95%CI:23.6-42.3; 33/100 children). The only demographic factor significantly associated with RSV acquisition was age of six months and below (odds ratio: 7.54 (2.62, 23.36); p=0.000). Children who were concomitantly infected with malaria had a lower risk of RSV infection (odds ratio: 0.38 (0.14, 0.95; P = 0.03). Conclusions: The RSV burden is high among children less than two years with ARI in the littoral region of Cameroon. There is a need for an effective public health RSV surveillance system with standard laboratory techniques and equipment to better understand the RSV disease age-specific incidence, seasonality, risk factors and RSV burden among patients in communities in Cameroon.

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Section: Discussionsupporting

confidence: 89%

Seroepidemiology of Respiratory Syncytial Virus infection in rural and semi-rural areas of the Littoral Region of Cameroon

Mandi

Yimer²,

Bekolo

et al. 2020

Preprint

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“…The mice then began CRA sensitization and challenge as previously described. 14,30,31 Briefly, mice were sensitized with 500 protein nitrogen units (PNU) of CRA on days 0, 1, and 2 and challenged with 500 PNU on days 14, 20, 22, and 23. Clinical-grade CRA (as used in skin testing) was used for these experiments.…”

Section: Cockroach Antigen (Cra) Modelmentioning

confidence: 99%

Inhibition of uric acid or IL‐1β ameliorates respiratory syncytial virus immunopathology and development of asthma

Schuler

Malinczak

Best

et al. 2020

Allergy

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Background Respiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown. Objective To investigate the role of uric acid (UA) and IL‐1β in RSV immunopathology and asthma predisposition. Methods Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro‐IL‐1β mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6‐7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL‐1 receptor antagonist was administered during RSV infection. Results Human tracheal aspirates from RSV‐infected infants showed elevated pro‐IL‐1β mRNA and protein. Inhibition of UA or IL‐1β during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL‐1β during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen. Conclusions Inhibiting UA and IL‐1β during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen‐induced asthma, and presents new therapeutic targets to reduce early‐life viral‐induced asthma development.

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“…Lung sections were stained with hematoxylin and eosin (HE) and periodic acid schiff (PAS). Slides were examined in a blinded fashion by three experienced observers, as previously described [15,16]. For each slide, ten randomly chosen areas were scored.…”

Section: Histological Examination Of Lung Sectionsmentioning

confidence: 99%

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

et al. 2019

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Objective Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. Methods Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. Results Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. Conclusions HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.

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Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease

Cited by 71 publications

References 73 publications

Seroepidemiology of Respiratory Syncytial Virus infection in rural and semi-rural areas of the Littoral Region of Cameroon

Seroepidemiology of Respiratory Syncytial Virus infection in rural and semi-rural areas of the Littoral Region of Cameroon

Inhibition of uric acid or IL‐1β ameliorates respiratory syncytial virus immunopathology and development of asthma

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

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