Could blocking an immune signal make virus-triggered allergic airway problems worse in mice?

Details

Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation—the combined OVA/RSV model—had greater AR than mice exposed to OVA alone or RSV alone. Interleukin 17A (IL-17A) was increased only in the OVA/RSV mice. The study aimed to determine whether IL-17A increases AR and inflammation in this combined model.

In this controlled experimental mouse study, wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or combined OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were collected after infection. Cytokine expression in the lungs or BAL fluid was measured by ELISA. MLNs were restimulated with either OVA (323-229) peptide or RSV M2 (127-135) peptide, and IL-17A protein expression was analysed. AR was measured using a methacholine challenge.

RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had lower interferon-β protein expression than RSV mice. They also had higher IL-23p19 mRNA expression in lung homogenates than mock, OVA or RSV mice.

Unexpectedly, IL-17A KO OVA/RSV mice had greater AR than WT OVA/RSV mice. The KO OVA/RSV mice also had more eosinophils and lymphocytes, and higher IL-13 protein expression, in BAL fluid than WT OVA/RSV mice.

The authors concluded that IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. Because IL-17A has been identified as a potential therapeutic target in asthma, they cautioned that inhibiting it during virally induced asthma exacerbations may have adverse consequences.