Macrophage LC3-associated phagocytosis is an immune defense against <i>Streptococcus pneumoniae</i> that diminishes with host aging

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  • Megumi Inomata
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
  • Shuying Xu
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
  • Pallavi Chandra
    Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110;
  • Simin N. Meydani
    Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111;
  • Genzou Takemura
    Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, 501-0296 Gifu, Japan
  • Jennifer A. Philips
    Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110;
  • John M. Leong
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;

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<jats:title>Significance</jats:title> <jats:p> The elderly exhibit susceptibility to many infectious agents, including <jats:italic>S. pneumoniae</jats:italic> . A robust acute inflammatory response to <jats:italic>S. pneumoniae</jats:italic> is associated with severe disease. <jats:italic>S. pneumoniae</jats:italic> 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 <jats:italic>S. pneumoniae</jats:italic> and modulate inflammation. Notably, compared to young BMDMs, aged BMDMs were deficient in LAP, resulting in compromised bacterial killing and enhanced proinflammatory responses. Thus, <jats:italic>S. pneumoniae</jats:italic> 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. </jats:p>

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