Subcutaneous BCG vaccination protects against streptococcal pneumonia via regulating innate immune responses in the lung

Abstract

Bacillus Calmette‐Guérin (BCG) still remains the only licensed vaccine for TB and has been shown to provide nonspecific protection against unrelated pathogens. This has been attributed to the ability of BCG to modulate the innate immune system, known as trained innate immunity (TII). Trained innate immunity is associated with innate immune cells being in a hyperresponsive state leading to enhanced host defense against heterologous infections. Both epidemiological evidence and prospective studies demonstrate cutaneous BCG vaccine‐induced TII provides enhanced innate protection against heterologous pathogens. Regardless of the extensive progress made thus far, the effect of cutaneous BCG vaccination against heterologous respiratory bacterial infections and the underlying mechanisms still remain unknown. Here, we show that s.c. BCG vaccine‐induced TII provides enhanced heterologous innate protection against pulmonary Streptococcus pneumoniae infection. We further demonstrate that this enhanced innate protection is mediated by enhanced neutrophilia in the lung and is independent of centrally trained circulating monocytes. New insight from this study will help design novel effective vaccination strategies against unrelated respiratory bacterial pathogens. image Subcutaneous BCG vaccine‐induced trained innate immunity in the lung provides enhanced heterologous innate protection against pulmonary Streptococcus pneumoniae infection. This enhanced protection is mediated by increased neutrophilia in the lung and is independent of trained circulating monocytes. Subcutaneous BCG vaccination protects against pulmonary S. pneumoniae infection. Augmented neutrophilia in the lung of BCG‐vaccinated hosts plays a critical role in enhanced protection. Trained circulating monocytes do not contribute to enhanced heterologous protection in the lung of BCG‐vaccinated hosts.