Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice
Open accessAbstract
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.
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Stimulation of CCL2 by macrophages upon pneumococcal infection alone requires expression of pneumolysin.
“Stimulation of CCL2 by macrophages upon pneumococcal infection alone required the pattern recognition receptor Nod2 and expression of the pore-forming toxin pneumolysin.”
From Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice (2011) · cites this paper as [17]
Stimulation of CCL2 by macrophages upon pneumococcal infection alone requires Nod2.
“Stimulation of CCL2 by macrophages upon pneumococcal infection alone required the pattern recognition receptor Nod2 and expression of the pore-forming toxin pneumolysin.”
From Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice (2011) · cites this paper as [17]
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Self-citation
- Authors
- Davis, K. M., Nakamura, S., & Weiser, J. N.
- Affiliations
- University of Pennsylvania (US)
- Nagasaki University (JP)
- Corresponding author
- Weiser, Jeffrey N.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-09-01
- Volume
- 121
- Issue
- 9
- Pages
- 3666-3676
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3163965
- OpenAlex
- W2160611039
- Cited by
- 190
- References
- 74
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 15 · 2019: 16 · 2018: 11 · 2017: 17 · 2016: 11 · 2015: 23 · 2014: 29 · 2013: 12 · 2012: 15
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (R01AI038446, AI 38446, R21AI044231, R01AI044231, AI44231, R37AI038446)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK50306, P30DK050306)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- NOD2, lysozyme, Streptococcus pneumoniae, pneumococcal carriage, macrophage recruitment, monocyte recruitment, CCR2, MCP-1, pneumolysin, innate immune recognition, adaptive immune response, intranasal infection, upper respiratory tract
- MeSH terms
- Animals, Humans, Macrophages, Mice, Inbred C57BL, Muramidase, Peptidoglycan, Phagocytes, Pneumococcal Infections, Streptococcus pneumoniae, Mice, Knockout, Chemokine CCL2, Toll-Like Receptor 2, Mice, Nod2 Signaling Adaptor Protein, Receptors, CCR2, Adaptive Immunity
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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