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Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness.

Publication ,  Journal Article
Schneider, D; Hong, JY; Popova, AP; Bowman, ER; Linn, MJ; McLean, AM; Zhao, Y; Sonstein, J; Bentley, JK; Weinberg, JB; Lukacs, NW; Curtis, JL ...
Published in: J Immunol
March 15, 2012

Recent studies link early rhinovirus (RV) infections to later asthma development. We hypothesized that neonatal RV infection leads to an IL-13-driven asthma-like phenotype in mice. BALB/c mice were inoculated with RV1B or sham on day 7 of life. Viral RNA persisted in the neonatal lung up to 7 d postinfection. Within this time frame, IFN-α, -β, and -γ peaked 1 d postinfection, whereas IFN-λ levels persisted. Next, we examined mice on day 35 of life, 28 d after initial infection. Compared with sham-treated controls, virus-inoculated mice demonstrated airways hyperresponsiveness. Lungs from RV-infected mice showed increases in several immune cell populations, as well as the percentages of CD4-positive T cells expressing IFN-γ and of NKp46/CD335(+), TCR-β(+) cells expressing IL-13. Periodic acid-Schiff and immunohistochemical staining revealed mucous cell metaplasia and muc5AC expression in RV1B- but not sham-inoculated lungs. Mucous metaplasia was accompanied by induction of gob-5, MUC5AC, MUC5B, and IL-13 mRNA. By comparison, adult mice infected with RV1B showed no change in IL-13 expression, mucus production, or airways responsiveness 28 d postinfection. Intraperitoneal administration of anti-IL-13 neutralizing Ab attenuated RV-induced mucous metaplasia and methacholine responses, and IL-4R null mice failed to show RV-induced mucous metaplasia. Finally, neonatal RV increased the inflammatory response to subsequent allergic sensitization and challenge. We conclude that neonatal RV1B infection leads to persistent airways inflammation, mucous metaplasia, and hyperresponsiveness, which are mediated, at least in part, by IL-13.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2012

Volume

188

Issue

6

Start / End Page

2894 / 2904

Location

United States

Related Subject Headings

  • Respiratory Mucosa
  • Respiratory Hypersensitivity
  • Real-Time Polymerase Chain Reaction
  • Picornaviridae Infections
  • Mice, Inbred BALB C
  • Mice
  • Metaplasia
  • Inflammation
  • Immunology
  • Immunohistochemistry
 

Citation

APA
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ICMJE
MLA
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Schneider, D., Hong, J. Y., Popova, A. P., Bowman, E. R., Linn, M. J., McLean, A. M., … Hershenson, M. B. (2012). Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness. J Immunol, 188(6), 2894–2904. https://doi.org/10.4049/jimmunol.1101391
Schneider, Dina, Jun Y. Hong, Antonia P. Popova, Emily R. Bowman, Marisa J. Linn, Alan M. McLean, Ying Zhao, et al. “Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness.J Immunol 188, no. 6 (March 15, 2012): 2894–2904. https://doi.org/10.4049/jimmunol.1101391.
Schneider D, Hong JY, Popova AP, Bowman ER, Linn MJ, McLean AM, et al. Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness. J Immunol. 2012 Mar 15;188(6):2894–904.
Schneider, Dina, et al. “Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness.J Immunol, vol. 188, no. 6, Mar. 2012, pp. 2894–904. Pubmed, doi:10.4049/jimmunol.1101391.
Schneider D, Hong JY, Popova AP, Bowman ER, Linn MJ, McLean AM, Zhao Y, Sonstein J, Bentley JK, Weinberg JB, Lukacs NW, Curtis JL, Sajjan US, Hershenson MB. Neonatal rhinovirus infection induces mucous metaplasia and airways hyperresponsiveness. J Immunol. 2012 Mar 15;188(6):2894–2904.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2012

Volume

188

Issue

6

Start / End Page

2894 / 2904

Location

United States

Related Subject Headings

  • Respiratory Mucosa
  • Respiratory Hypersensitivity
  • Real-Time Polymerase Chain Reaction
  • Picornaviridae Infections
  • Mice, Inbred BALB C
  • Mice
  • Metaplasia
  • Inflammation
  • Immunology
  • Immunohistochemistry