MyD88-dependent protective mechanism of alveolar macrophages induced by Bacillus subtilis spore in mice infected with respiratory syncytial virus A2

Abstract

Respiratory syncytial virus (RSV) is one of the most common respiratory diseases in children and elderly who are immune-compromised. Although induction of successful innate immunity is critical for the protection against viral infection, specific role and defense mechanism of alveolar macrophages (AMs) in RSV infection are yet to be illuminated. Therefore, the objective of the present study was to elucidate the exact role of AMs activated with Bacillus subtilis spore in mice infected with RSV. The results showed that AMs played a pivotal role in the protection during the initial stage of RSV infection and that the administration of spore derived from Bacillus subtilis induced activation of AM population coincident with enhancing antiviral effector molecules, GM-CSF and classically activated macrophages (M1 macrophage)-related genes. Furthermore, these protective immune responses were dependent on MyD88 signaling pathway in the AMs. Pre-treatment with spore through intranasal route induced protective immunity in mice infected with RSV as shown by significantly low viral load at 4 days post infection. It was noting that spore-treated mice displayed the increase of AMs, but not neutrophils or inflammatory monocytes after the infection. Also, these mice showed notably increased level of IFN-β and IL-12p40. When AMs were depleted, mice became intensified the disease severity as shown by persisted high level of viral load with increased pathology scores of pulmonary in the lung resulting a very weak protective efficiency against RSV infection. These results suggest that AMs treated with spore are indispensable for the effective protection against RSV infection. Furthermore, MyD88-/- mice were unable to induce protective responses regardless of spore treatment, suggesting that the protection by spore-treated AMs was mediated through MyD88-dependent signaling pathway. In conclusion, I revealed that administration of spore via intranasal route led to the early activation of AMs via MyD88-dependent pathway is responsible for the protective immunity in mice infected with RSV.