Heat-killed Staphylococcus aureus reduces atherosclerosis by inducing anti-inflammatory macrophages.

Autor: Frodermann V; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., van Duijn J; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., van Puijvelde GH; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., van Santbrink PJ; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Lagraauw HM; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., de Vries MR; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Quax PH; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Bot I; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Foks AC; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., de Jager SC; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.; Laboratory for Experimental Cardiology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Kuiper J; Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of internal medicine [J Intern Med] 2016 Jun; Vol. 279 (6), pp. 592-605. Date of Electronic Publication: 2016 Feb 23.
DOI: 10.1111/joim.12484
Abstrakt: Background: Staphylococcus aureus cell wall components can induce IL-10 responses by immune cells, which may be atheroprotective. Therefore, in this study, we investigated whether heat-killed S. aureus (HK-SA) could inhibit the development of atherosclerosis.
Methods: Atherosclerosis-susceptible LDL receptor-deficient mice were administered intraperitoneal HK-SA twice weekly and fed a Western-type diet for 6 weeks.
Results: HK-SA administration resulted in a 1.6-fold increase in IL-10 production by peritoneal macrophages and splenocytes, and a 12-fold increase in serum IL-10 levels. Moreover, aortic plaque ICAM-1, VCAM-1 and CCL2 expression levels were significantly downregulated by on average 40%. HK-SA-treated mice had reduced numbers of inflammatory Ly-6C(hi) monocytes as well as Th1 and Th17 cells in the circulation and spleen, respectively. Attenuated leucocyte recruitment resulted in a significant inhibition of macrophage and T cell infiltration in atherosclerotic plaques, culminating in a significant 34% reduction in the development of atherosclerosis. To determine the effects of intraperitoneal HK-SA treatment, we stimulated macrophages with HK-SA in vitro. This resulted in a significant toll-like receptor 2 (TLR2)-dependent increase in IL-10, arginase-1, iNOS, TNF-α, PD-L1, CCL22 and indoleamine 2,3-dioxygenase expression. It was found that phosphoinositide 3-kinase crucially determined the balance of pro- and anti-inflammatory gene expression. The HK-SA-induced macrophage phenotype resembled M2b-like immunoregulatory macrophages.
Conclusions: We have shown that HK-SA treatment induces strong anti-inflammatory IL-10 responses by macrophages, which are largely dependent on TLR2 and PI3K, and protects against the development of atherosclerosis. Commensalism with S. aureus could thus reduce cardiovascular events.
(© 2016 The Association for the Publication of the Journal of Internal Medicine.)
Databáze: MEDLINE
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