The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome
| Autor: | Youngji Cho, Stephanie A. Shore, David I. Kasahara, Curtis Huttenhower, Jeremy E. Wilkinson, A.P. Cardoso |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Biology Gut flora Airway responsiveness Mice 03 medical and health sciences Ozone 0302 clinical medicine Sex differences Respiratory Hypersensitivity medicine Animals Weaning Microbiome Receptor Lung Interleukin 5 Mice Knockout lcsh:RC705-779 Inhalation Exposure medicine.diagnostic_test Microbiota Research Neutrophil lcsh:Diseases of the respiratory system Interleukin-33 biology.organism_classification Interleukin-1 Receptor-Like 1 Protein 3. Good health Mice Inbred C57BL Interleukin 33 030104 developmental biology Bronchoalveolar lavage Cytokine 030228 respiratory system Immunology IL-33 Female Interleukin-5 |
| Zdroj: | Respiratory Research, Vol 20, Iss 1, Pp 1-15 (2019) Respiratory Research |
| ISSN: | 1465-993X |
| DOI: | 10.1186/s12931-019-1168-x |
| Popis: | Background Interleukin-33 is released in the airways following acute ozone exposure and has the ability to cause airway hyperresponsiveness, a defining feature of asthma. Ozone causes greater airway hyperresponsiveness in male than female mice. Moreover, sex differences in the gut microbiome account for sex differences in this response to ozone. The purpose of this study was to determine whether there were sex differences in the role of interleukin-33 in ozone-induced airway hyperresponsiveness and to examine the role of the microbiome in these events. Methods Wildtype mice and mice genetically deficient in ST2, the interleukin-33 receptor, were housed from weaning with either other mice of the same genotype and sex, or with mice of the same sex but opposite genotype. At 15 weeks of age, fecal pellets were harvested for 16S rRNA sequencing and the mice were then exposed to air or ozone. Airway responsiveness was measured and a bronchoalveolar lavage was performed 24 h after exposure. Results In same-housed mice, ozone-induced airway hyperresponsiveness was greater in male than female wildtype mice. ST2 deficiency reduced ozone-induced airway hyperresponsiveness in male but not female mice and abolished sex differences in the response to ozone. However, sex differences in the role of interleukin-33 were unrelated to type 2 cytokine release: ozone-induced increases in bronchoalveolar lavage interleukin-5 were greater in females than males and ST2 deficiency virtually abolished interleukin-5 in both sexes. Since gut microbiota contribute to sex differences in ozone-induced airway hyperresponsiveness, we examined the role of the microbiome in these ST2-dependent sex differences. To do so, we cohoused wildtype and ST2 deficient mice, a situation that allows for transfer of microbiota among cage-mates. Cohousing altered the gut microbial community structure, as indicated by 16S rRNA gene sequencing of fecal DNA and reversed the effect of ST2 deficiency on pulmonary responses to ozone in male mice. Conclusions The data indicate that the interleukin-33 /ST2 pathway contributes to ozone-induced airway hyperresponsiveness in male mice and suggest that the role of interleukin-33 is mediated at the level of the gut microbiome. Electronic supplementary material The online version of this article (10.1186/s12931-019-1168-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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