Cited by 274Inflammasome and immune disordersImmune Response and InflammationStreptococcal Infections and Treatments

Staphylococcus aureus Evades Lysozyme-Based Peptidoglycan Digestion that Links Phagocytosis, Inflammasome Activation, and IL-1β Secretion

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Shimada, Takahiro, Park, Bong Goo, Wolf, Andrea J., Brikos, Constantinos, Goodridge, Helen S., Becker, Courtney A., Reyes, Christopher N., Miao, Edward A. +4 more·2010·Cell Host & Microbe

Abstract

IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wall component peptidoglycan (PGN) must be particulate and internalized via phagocytosis to activate NLRP3 inflammasomes and IL-1beta secretion. In the context of S. aureus infection of macrophages, we find that phagocytosis and lysozyme-based bacterial cell wall degradation are necessary to induce IL-1beta secretion. Further, an S. aureus enzyme, PGN O-acetyltransferase A, previously demonstrated to make cell wall PGN resistant to lysozyme, strongly suppresses inflammasome activation and inflammation in vitro and in vivo. These observations demonstrate that phagocytosis and lysozyme-based cell wall degradation of S. aureus are functionally coupled to inflammasome activation and IL-1beta secretion and illustrate a case whereby a bacterium specifically subverts IL-1beta secretion through chemical modification of its cell wall PGN.

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Crossref · 10.1016/j.chom.2009.12.008

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  • Keratinocytes are primed for inflammasome activation by surface contact with staphylococci because they constitutively express IL-1β, unlike macrophages which require internalization of peptidoglycan.

    “In contrast to macrophages, which require the internalization of particulate peptidoglycan to activate inflammasome signaling [17], keratinocytes constitutively express IL-1β and thus are primed for activation by surface contact with staphylococci.”

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Authors
Shimada, T., Park, B. G., Wolf, A. J., Brikos, C., Goodridge, H. S., Becker, C. A., Reyes, C. N., Miao, E. A., Aderem, A., Götz, F., Liu, G. Y., & Underhill, D. M.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Institute for Systems Biology (US)
  • University of Tübingen (DE)
Corresponding author
Underhill, David M.
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2010-01
Volume
7
Issue
1
Pages
38-49
ISSN
1931-3128 (ISSN-L)
OpenAlex
W2064358027
Cited by
274
References
65
Citations by year
2026: 9 · 2025: 12 · 2024: 13 · 2023: 12 · 2022: 17 · 2021: 17 · 2020: 11 · 2019: 18 · 2018: 21 · 2017: 13 · 2016: 20 · 2015: 20 · 2014: 13 · 2013: 17 · 2012: 26
FWCI
10.16
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Genentech
  • National Institute of General Medical Sciences (GM-085796, R01GM085796)
  • National Institute of Allergy and Infectious Diseases (R01AI025032)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
Keywords
Staphylococcus aureus, peptidoglycan, lysozyme, phagocytosis, NLRP3 inflammasome, IL-1β secretion, macrophages, inflammation, bacterial evasion of host defense
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Bacterial Proteins, Carrier Proteins, Macrophages, Models, Biological, Muramidase, Peptidoglycan, Phagosomes, Staphylococcus aureus, Interleukin-1beta

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