Early-life Heterologous Rhinovirus Infections Induce an Exaggerated Asthma-Like Phenotype
dc.contributor.author | Rajput, C | |
dc.contributor.author | Han, M | |
dc.contributor.author | Ishikawa, T | |
dc.contributor.author | Lei, J | |
dc.contributor.author | Jazaeri, S | |
dc.contributor.author | Bentley, JK | |
dc.contributor.author | Hershenson, MB | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-01-18T18:52:52Z | |
dc.date.available | 2024-01-18T18:52:52Z | |
dc.date.issued | 2020-04-25 | |
dc.identifier.issn | 0091-6749 | |
dc.identifier.issn | 1097-6825 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/32344055 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/192078 | en |
dc.description.abstract | Background: Early-life wheezing-associated respiratory tract infection by rhinovirus (RV) is a risk factor for asthma development. Infants are infected with many different RV strains per year. Objective: We previously showed that RV infection of 6-day-old BALB/c mice induces a mucous metaplasia phenotype that is dependent on type 2 innate lymphoid cells (ILC2s). We hypothesized that early-life RV infection alters the response to subsequent heterologous infection, inducing an exaggerated asthma-like phenotype. Methods: Wild-type BALB/c mice and Rorafl/flIl7rcre mice lacking ILC2s were treated as follows: (1) sham on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 plus RV-A2 on day 13, and (4) RV-A1B on day 6 plus RV-A2 on day 13. Results: Mice infected with RV-A1B at day 6 and sham at day 13 showed an increased number of bronchoalveolar lavage eosinophils and increased expression of IL-13 mRNA but not expression of IFN-γ mRNA (which is indicative of a type 2 immune response), whereas mice infected with sham on day 6 and RV-A2 on day 13 of life demonstrated increased IFN-γ expression (which is a mature antiviral response). In contrast, mice infected with RV-A1B on day 6 before RV-A2 infection on day 13 showed increased expression of IL-13, IL-5, Gob5, Muc5b, and Muc5ac mRNA; increased numbers of eosinophils and IL-13–producing ILC2s; and exaggerated mucus metaplasia and airway hyperresponsiveness. Compared with Rorafl/fl mice, Rorafl/flIl7rcre mice showed complete suppression of bronchoalveolar lavage eosinophils and mucous metaplasia. Conclusion: Early-life RV infection alters the response to subsequent heterologous infection, inducing an intensified asthma-like phenotype that is dependent on ILC2s. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.subject | Asthma | |
dc.subject | IL-13 | |
dc.subject | ILC2 | |
dc.subject | RV-A1B | |
dc.subject | RV-A2 | |
dc.subject | childhood | |
dc.subject | early-life | |
dc.subject | rhinovirus | |
dc.subject | trained immunity | |
dc.subject | type 2 innate lymphoid cell | |
dc.subject | Adverse Childhood Experiences | |
dc.subject | Animals | |
dc.subject | Animals, Newborn | |
dc.subject | Asthma | |
dc.subject | Disease Progression | |
dc.subject | Eosinophils | |
dc.subject | Humans | |
dc.subject | Immunity, Innate | |
dc.subject | Infant, Newborn | |
dc.subject | Interleukin-13 | |
dc.subject | Mice | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Phenotype | |
dc.subject | Picornaviridae Infections | |
dc.subject | Respiratory Sounds | |
dc.subject | Rhinovirus | |
dc.subject | Th2 Cells | |
dc.title | Early-life Heterologous Rhinovirus Infections Induce an Exaggerated Asthma-Like Phenotype | |
dc.type | Article | |
dc.identifier.pmid | 32344055 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/192078/2/1-s2.0-S0091674920305509-main.pdf | |
dc.identifier.doi | 10.1016/j.jaci.2020.03.039 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22078 | |
dc.identifier.source | J Allergy Clin Immunol. | |
dc.description.version | Published version | |
dc.date.updated | 2024-01-18T18:52:40Z | |
dc.identifier.orcid | 0000-0001-8865-7979 | |
dc.identifier.orcid | 0000-0001-9436-5593 | |
dc.description.filedescription | Description of 1-s2.0-S0091674920305509-main.pdf : Published version | |
dc.identifier.volume | 146 | |
dc.identifier.issue | 3 | |
dc.identifier.startpage | 571 | |
dc.identifier.endpage | 582 | |
dc.identifier.name-orcid | Rajput, C | |
dc.identifier.name-orcid | Han, M | |
dc.identifier.name-orcid | Ishikawa, T | |
dc.identifier.name-orcid | Lei, J | |
dc.identifier.name-orcid | Jazaeri, S | |
dc.identifier.name-orcid | Bentley, JK; 0000-0001-8865-7979 | |
dc.identifier.name-orcid | Hershenson, MB; 0000-0001-9436-5593 | |
dc.working.doi | 10.7302/22078 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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