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Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation

Kasetty, Gopinath LU ; Bhongir, Ravi K.V. LU ; Papareddy, Praveen LU ; Tufvesson, Ellen LU ; Stenberg, Henning LU ; Bjermer, Leif LU ; Hultgårdh-Nilsson, Anna LU ; Herwald, Heiko LU and Egesten, Arne LU (2018) In Allergy: European Journal of Allergy and Clinical Immunology
Abstract

Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1+/+) and OPN knockout (Spp1−/−) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from... (More)

Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1+/+) and OPN knockout (Spp1−/−) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1−/− mice than in Spp1+/+ mice. Moreover, OPN-deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1+/+ mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1−/− mice. Furthermore, Spp1−/− mice had higher levels of cytokines and immune cells in BALF than did Spp1+/+ mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
allergy, asthma, host defense, house dust mite, osteopontin, Streptococcus pneumoniae
in
Allergy: European Journal of Allergy and Clinical Immunology
publisher
Wiley-Blackwell
external identifiers
  • scopus:85056765715
ISSN
0105-4538
DOI
10.1111/all.13646
language
English
LU publication?
yes
id
7666727d-bd6f-45d5-b6f9-09671aff1e26
date added to LUP
2018-11-28 11:04:46
date last changed
2019-02-18 10:29:04
@article{7666727d-bd6f-45d5-b6f9-09671aff1e26,
  abstract     = {<p>Background: In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1<sup>+/+</sup>) and OPN knockout (Spp1<sup>−/−</sup>) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1<sup>−/−</sup> mice than in Spp1<sup>+/+</sup> mice. Moreover, OPN-deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1<sup>+/+</sup> mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1<sup>−/−</sup> mice. Furthermore, Spp1<sup>−/−</sup> mice had higher levels of cytokines and immune cells in BALF than did Spp1<sup>+/+</sup> mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma.</p>},
  author       = {Kasetty, Gopinath and Bhongir, Ravi K.V. and Papareddy, Praveen and Tufvesson, Ellen and Stenberg, Henning and Bjermer, Leif and Hultgårdh-Nilsson, Anna and Herwald, Heiko and Egesten, Arne},
  issn         = {0105-4538},
  keyword      = {allergy,asthma,host defense,house dust mite,osteopontin,Streptococcus pneumoniae},
  language     = {eng},
  month        = {10},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy: European Journal of Allergy and Clinical Immunology},
  title        = {Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation},
  url          = {http://dx.doi.org/10.1111/all.13646},
  year         = {2018},
}