Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation.

Abstract

BACKGROUND:

Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation.

METHODS:

Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry.

RESULTS:

While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well.

CONCLUSIONS:

Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.

• Authors: Kristi J Warren, Jill A Poole, Jenea M Sweeter, Jane M DeVasure, John D Dickinson, R Stokes Peebles Jr, Todd A Wyatt
• Journal: Respiratory research (Respir Res) Vol. 22 Issue 1 Pg. 206 (Jul 15 2021) ISSN: 1465-993X [Electronic] England
• PMID: 34266437 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Il33 protein, mouse
• Interleukin-33
• Ovalbumin

Topics

• Animals
• Asthma (chemically induced, immunology, metabolism, virology)
• Female
• Interleukin-33 (immunology, metabolism)
• Lymphocytes (immunology, metabolism, virology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (toxicity)
• Respiratory Syncytial Virus Infections (immunology, metabolism)
• Respiratory Syncytial Viruses