Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo

Lance R. Thurlow, Mark L. Hanke, Teresa Fritz, Amanda Angle, Amy Aldrich, Stetson H. Williams, Ian L. Engebretsen, Kenneth W Bayles, Alexander R. Horswill, Tammy L Kielian

Research output: Contribution to journalArticle

273 Citations (Scopus)

Abstract

Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remain to be defined. We used a mouse model of catheter-associated biofilm infection to assess the functional importance of TLR2 and TLR9 in the host immune response during biofilm formation, because ligands for both receptors are present within the biofilm. Interestingly, neither TLR2 nor TLR9 impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1β, TNF-α, CXCL2, and CCL2 expression during biofilm infection compared with the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in inducible NO synthase expression concomitant with robust arginase-1 induction. Coculture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host. Copyright

Original languageEnglish (US)
Pages (from-to)6585-6596
Number of pages12
JournalJournal of Immunology
Volume186
Issue number11
DOIs
StatePublished - Jun 1 2011

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Biofilms
Phagocytosis
Staphylococcus aureus
Macrophages
Inflammation
Infection
Catheter-Related Infections
Arginase
Growth
Coculture Techniques
Interleukin-1
Innate Immunity
Nitric Oxide Synthase
Wound Healing
Polysaccharides
Catheters

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. / Thurlow, Lance R.; Hanke, Mark L.; Fritz, Teresa; Angle, Amanda; Aldrich, Amy; Williams, Stetson H.; Engebretsen, Ian L.; Bayles, Kenneth W; Horswill, Alexander R.; Kielian, Tammy L.

In: Journal of Immunology, Vol. 186, No. 11, 01.06.2011, p. 6585-6596.

Research output: Contribution to journalArticle

Thurlow, LR, Hanke, ML, Fritz, T, Angle, A, Aldrich, A, Williams, SH, Engebretsen, IL, Bayles, KW, Horswill, AR & Kielian, TL 2011, 'Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo', Journal of Immunology, vol. 186, no. 11, pp. 6585-6596. https://doi.org/10.4049/jimmunol.1002794
Thurlow, Lance R. ; Hanke, Mark L. ; Fritz, Teresa ; Angle, Amanda ; Aldrich, Amy ; Williams, Stetson H. ; Engebretsen, Ian L. ; Bayles, Kenneth W ; Horswill, Alexander R. ; Kielian, Tammy L. / Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. In: Journal of Immunology. 2011 ; Vol. 186, No. 11. pp. 6585-6596.
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