TY - JOUR
T1 - Candida albicans Primes TLR Cytokine Responses through a Dectin-1/Raf-1–Mediated Pathway
AU - Ifrim, Daniela C.
AU - Joosten, Leo A. B.
AU - Kullberg, Bart-Jan
AU - Jacobs, Liesbeth
AU - Jansen, Trees
AU - Williams, David L.
AU - Gow, Neil A. R.
AU - Van Der Meer, Jos W. M.
AU - Netea, Mihai G.
AU - Quintin, Jessica
N1 - D.C.I. was supported by funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement HEALTH-2010-260338 (Fungi in the Setting of Inflammation, Allergy and Autoimmune Diseases: Translating Basic Science into Clinical Practices). J.Q. and M.G.N. were supported by a Vici Grant of The Netherlands Organization for Scientific Research (to M.G.N.). This work was supported in part by National Institutes of Health (Grant GM53522 to D.L.W.). N.A.R.G. was supported by The Wellcome Trust.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - The immune system is essential to maintain homeostasis with resident microbial populations, ensuring that the symbiotic host-microbial relationship is maintained. In parallel, commensal microbes significantly shape mammalian immunity at the host mucosal surface, as well as systemically. Candida albicans is an opportunistic pathogen that lives as a commensal on skin and mucosa of healthy individuals. Little is known about its capacity to modulate responses toward other microorganisms, such as colonizing bacteria (e.g., intestinal microorganisms). The aim of this study was to assess the cytokine production of PBMCs induced by commensal bacteria when these cells were primed by C. albicans. We show that C. albicans and β-1,3-glucan induce priming of human primary mononuclear cells and this leads to enhanced cytokine production upon in vitro stimulation with TLR ligands and bacterial commensals. This priming requires the β-1,3-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. In addition, although purified mannans cannot solely mediate the priming, the presence of mannosyl residues in the cell wall of C. albicans is nevertheless required. In conclusion, C. albicans is able to modify cytokine responses to TLR ligands and colonizing bacteria, which is likely to impact the inflammatory reaction during mucosal diseases.
AB - The immune system is essential to maintain homeostasis with resident microbial populations, ensuring that the symbiotic host-microbial relationship is maintained. In parallel, commensal microbes significantly shape mammalian immunity at the host mucosal surface, as well as systemically. Candida albicans is an opportunistic pathogen that lives as a commensal on skin and mucosa of healthy individuals. Little is known about its capacity to modulate responses toward other microorganisms, such as colonizing bacteria (e.g., intestinal microorganisms). The aim of this study was to assess the cytokine production of PBMCs induced by commensal bacteria when these cells were primed by C. albicans. We show that C. albicans and β-1,3-glucan induce priming of human primary mononuclear cells and this leads to enhanced cytokine production upon in vitro stimulation with TLR ligands and bacterial commensals. This priming requires the β-1,3-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. In addition, although purified mannans cannot solely mediate the priming, the presence of mannosyl residues in the cell wall of C. albicans is nevertheless required. In conclusion, C. albicans is able to modify cytokine responses to TLR ligands and colonizing bacteria, which is likely to impact the inflammatory reaction during mucosal diseases.
UR - http://www.scopus.com/inward/record.url?scp=84876009100&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1202611
DO - 10.4049/jimmunol.1202611
M3 - Article
C2 - 23475217
AN - SCOPUS:84876009100
SN - 0022-1767
VL - 190
SP - 4129
EP - 4135
JO - The Journal of Immunology
JF - The Journal of Immunology
IS - 8
ER -