Respiratory syncytial virus enhances respiratory allergy in mice despite the inhibitory effect of virus‐induced interferon‐γ

Abstract

In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic Th2 immune response, characterised by production of interleukin (IL)-4, IL-5, and IL-13, and eosinophilic inflammation. This enhancement of the Th2 response occurs simultaneously with a strong RSV-induced Th1 cytokine response (IL-12 and IFN-gamma). The present study investigated whether IFN-gamma and IL-12 are critically involved in this RSV-enhanced OVA allergy. Therefore, IFN-gammaR- and IL-12-deficient mice (both on a 129/Sv/Ev background) were sensitised and challenged with ovalbumin (OVA) and infected with RSV during the OVA challenge period. Neither gene deletion affected the development of ovalbumin-induced allergic inflammation in mice. However, when OVA-allergic IFN-gammaR deficient mice were infected with RSV, an increased pulmonary eosinophilic infiltrate and increased IL-4 and IL-13 mRNA expression in lung tissue were observed compared with identically treated wild-type mice. In contrast, deficiency of IL-12 did not aggravate the Th2 immune and inflammatory response in OVA/RSV-treated mice, compared with wild-type. In conclusion, the virus-induced IFN-gamma response diminishes the Th2 inflammatory response during OVA allergy but fails to prevent totally the enhancement of the OVA allergy by RSV. In contrast, IL-12 is not involved in inhibiting nor increasing the RSV-enhanced allergy in 129/Sv/Ev mice.

Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice

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Understanding the mechanisms of viral induced asthma: New therapeutic directions

“…These processes are essential in moderating eosinophil migration and IFN-γ and CD8+ cells are crucial for viral clearance. In the absence of IFN-γ a dominant Th2 response induces eosinophil influx of the lung and AHR (Barends et al, 2003). By contrast, the absence of IL-12 and IL-18 has little effect .…”

Immune Responses and Disease Enhancement during Respiratory Syncytial Virus Infection

“…CD8 T cells are a major source of IFN-␥. In the mouse model, IFN-␥ is produced following primary infection but not sufficiently to control RSV-induced allergy to OVA (12). The role of IFN-␥ in RSV disease is unclear; in the mouse model it has been shown to be necessary for protection (126), and airway obstruction is decreased in IFN-␥ knockout mice (175).…”