A Modulatory Interleukin-10 Response to Staphylococcal Peptidoglycan Prevents Th1/Th17 Adaptive Immunity to Staphylococcus aureus

Toll-like receptor (TLR) 2 on antigen-presenting cells (APCs) enables these cells to recognize peptidoglycanembedded lipopeptides and glycopolymers in the Staphylococcus aureus cell wall and mount an inflammatory response to this microbe. TLR2 signalling can also modulate immunity to S. aureus by in...

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Bibliographic Details
Published in:The Journal of infectious diseases 2011-07, Vol.204 (2), p.253-262
Main Authors: Frodermann, Vanessa, Chau, Thu A., Sayedyahossein, Samar, Toth, Judit M., Heinrichs, David E., Madrenas, Joaquín
Format: Article
Language:English
Subjects:
Adaptive Immunity
BACTERIA
Bacteriology
Biological and medical sciences
Cytokines
Dendritic cells
Elafin - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Infections
Infectious diseases
Interleukin-10 - immunology
Ligands
Macrophages
Macrophages - immunology
Medical sciences
Microbiology
Miscellaneous
Monocytes
Monocytes - immunology
Peptidoglycan - immunology
Staphylococcus
Staphylococcus aureus
Staphylococcus aureus - immunology
T lymphocytes
Th1 Cells - immunology
Th17 Cells - immunology
Toll like receptors
Toll-Like Receptor 2 - immunology
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Summary:Toll-like receptor (TLR) 2 on antigen-presenting cells (APCs) enables these cells to recognize peptidoglycanembedded lipopeptides and glycopolymers in the Staphylococcus aureus cell wall and mount an inflammatory response to this microbe. TLR2 signalling can also modulate immunity to S. aureus by inducing an interleukin (IL)—10 response in APCs. What determines the balance between proinflammatory and modulatory responses to S. aureus is unknown. We show that the modulatory IL-10 response preferentially occurs upon CD 14-and CD36-independent TLR2 signaling, triggering PI3K activation, and is restricted to monocytes and monocytederived macrophages (MФs). In contrast, monocyte-derived dendritic cells (DCs) produce mostly IL-12 and IL-23. The differential APC polarization induced by staphylococcal peptidoglycan translates into differential T helper responses: MФs primarily trigger IL-10 and weak IL-17 responses, whereas DCs trigger a robust Th1/Th17 response. Exploitation of TLR2 signalling plasticity by S. aureus may explain the wide range of outcomes of human encounters with this microbe.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jir276