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Citations to this article

Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice
Kimberly M. Davis, … , Shigeki Nakamura, Jeffrey N. Weiser
Kimberly M. Davis, … , Shigeki Nakamura, Jeffrey N. Weiser
Published August 15, 2011
Citation Information: J Clin Invest. 2011;121(9):3666-3676. https://doi.org/10.1172/JCI57761.
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Research Article

Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice

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Abstract

Streptococcus pneumoniae colonizes the mucosal surface of the human upper respiratory tract. A colonization event is gradually cleared through phagocytosis by monocytes/macrophages that are recruited to the airway lumen. Here, we sought to define the bacterial and host factors that promote monocyte/macrophage influx and S. pneumoniae clearance using intranasal bacterial challenge in mice. We found that the recruitment of monocytes/macrophages required their expression of the chemokine receptor CCR2 and correlated with expression of the CCR2 ligand CCL2. Production of CCL2 and monocyte/macrophage recruitment were deficient in mice lacking digestion of peptidoglycan by lysozyme (LysM) and cytosolic sensing of the products of digestion by Nod2. Ex vivo macrophages produced CCL2 following bacterial uptake, digestion by LysM, and sensing of peptidoglycan by Nod2. Sensing of digested peptidoglycan by Nod2 also required the pore-forming toxin pneumolysin. The generation of an adaptive immune response, as measured by anti-pneumococcal antibody titers, was also LysM- and Nod2-dependent. Together, our data suggest that bacterial uptake by professional phagocytes is followed by LysM-mediated digestion of S. pneumoniae–derived peptidoglycan, sensing of the resulting products by Nod2, release of the chemokine CCL2, and CCR2-dependent recruitment of the additional monocytes/macrophages required for the clearance of an S. pneumoniae colonization event.

Authors

Kimberly M. Davis, Shigeki Nakamura, Jeffrey N. Weiser

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 Total
Citations: 1 2 7 5 5 8 9 11 13 7 15 15 8 5 1 112
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JM Cohen, S Chimalapati, C Vogel, A Belkum, HE Baxendale, JS Brown
Vaccine 2012
MARCO Is Required for TLR2- and Nod2-Mediated Responses to Streptococcus pneumoniae and Clearance of Pneumococcal Colonization in the Murine Nasopharynx
MG Dorrington, AM Roche, SE Chauvin, Z Tu, KL Mossman, JN Weiser, DM Bowdish
Journal of immunology (Baltimore, Md. : 1950) 2012
Muramyl Dipeptide Induces NOD2-Dependent Ly6Chigh Monocyte Recruitment to the Lungs and Protects Against Influenza Virus Infection
F Coulombe, S Fiola, S Akira, Y Cormier, J Gosselin
PloS one 2012
Synergistic stimulation of type I interferons during influenza co-infection promotes Streptococcus pneumoniae colonization in mice
Shigeki Nakamura, Kimberly Davis, Jeffrey Weiser
Journal of Clinical Investigation 2011

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