TY - JOUR
T1 - Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes
AU - Quintin, Jessica
AU - Saeed, Sadia
AU - Martens, Joost H.A.
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Ifrim, Daniela C.
AU - Logie, Colin
AU - Jacobs, Liesbeth
AU - Jansen, Trees
AU - Kullberg, Bart Jan
AU - Wijmenga, Cisca
AU - Joosten, Leo A.B.
AU - Xavier, Ramnik J.
AU - Van Der Meer, Jos W.M.
AU - Stunnenberg, Hendrik G.
AU - Netea, Mihai G.
N1 - Funding Information:
J.Q. and M.G.N. were supported by a Vici Grant of the Netherlands Organization for Scientific Research (to M.G.N.). S.S. was supported by the Higher Education Commission of Pakistan and J.H.A.M. by a Vidi Grant of the Netherlands Organization for Scientific Research. D.C.I. was supported by the All-Fun EU-FP7 grant. C.L. was supported by the “DNA-in-action” consortium, Foundation for Fundamental Research on Matter (FOM), Netherlands Organisation for Scientific Research (NWO). R.J.X. was supported by grants (AI 062773, DK 043351 DK 83756) from the US National Institutes of Health and the Helmsley Trust. J.Q., S.S., C.W., J.H.A.M., C.L., J.W.M.v.d.M., and M.G.N. designed and analyzed the experiments. J.Q., S.S., M.G.N., E.J.G.-B., L.A.B.J., and T.J. performed the experiments. D.C.I. contributed to some of the experiments. J.Q., S.S., R.J.X., J.W.M.v.d.M., H.G.S., and M.G.N. wrote the manuscript, and all authors contributed to the manuscript preparation. M.G.N. supervised the project.
PY - 2012/8/16
Y1 - 2012/8/16
N2 - Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against reinfection. Testing this concept of "trained immunity," we show that mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner. C. albicans and fungal cell wall β-glucans induced functional reprogramming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the β-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. Monocyte training by β-glucans was associated with stable changes in histone trimethylation at H3K4, which suggests the involvement of epigenetic mechanisms in this phenomenon. The functional reprogramming of monocytes, reminiscent of similar NK cell properties, supports the concept of "trained immunity" and may be employed for the design of improved vaccination strategies.
AB - Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against reinfection. Testing this concept of "trained immunity," we show that mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner. C. albicans and fungal cell wall β-glucans induced functional reprogramming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the β-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. Monocyte training by β-glucans was associated with stable changes in histone trimethylation at H3K4, which suggests the involvement of epigenetic mechanisms in this phenomenon. The functional reprogramming of monocytes, reminiscent of similar NK cell properties, supports the concept of "trained immunity" and may be employed for the design of improved vaccination strategies.
UR - http://www.scopus.com/inward/record.url?scp=84865119423&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2012.06.006
DO - 10.1016/j.chom.2012.06.006
M3 - Article
C2 - 22901542
AN - SCOPUS:84865119423
SN - 1931-3128
VL - 12
SP - 223
EP - 232
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -