Macrophage LC3-associated phagocytosis is an immune defense against <i>Streptococcus pneumoniae</i> that diminishes with host aging
Megumi Inomata, Shuying Xu, Pallavi Chandra, Simin Nikbin Meydani, Genzou Takemura, Jennifer A. Philips, John M. Leong
Abstract
Significance The elderly exhibit susceptibility to many infectious agents, including S. pneumoniae . A robust acute inflammatory response to S. pneumoniae is associated with severe disease. S. pneumoniae triggers canonical autophagy in nonprofessional phagocytes, but its role in macrophages is largely unexplored. We found that BMDMs utilize LAP, rather than canonical autophagy, to both eliminate S. pneumoniae and modulate inflammation. Notably, compared to young BMDMs, aged BMDMs were deficient in LAP, resulting in compromised bacterial killing and enhanced proinflammatory responses. Thus, S. pneumoniae triggers LAP in BMDMs, a process that controls both microbial numbers and tissue-damaging inflammation. Importantly, LAP diminishes with age and may contribute to the observed susceptibility of the elderly to many infectious diseases.