Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes.
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.
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Jessica
J
Quintin
Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands.
Sadia
S
Saeed
Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands.
Joost H A
JHA
Martens
4th Department of Internal Medicine, University of Athens, Medical School, 12462 Athens, Greece.|Center for Sepsis Control and Care, Jena University Hospital, 07747 Jena, Germany.
Evangelos J
EJ
Giamarellos-Bourboulis
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Daniela C
DC
Ifrim
Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands.
Colin
C
Logie
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Liesbeth
L
Jacobs
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Trees
T
Jansen
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Bart-Jan
BJ
Kullberg
Department of Genetics, University Medical Center Groningen and University of Groningen, 9713 EX Groningen, The Netherlands.
Cisca
C
Wijmenga
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Leo A B
LAB
Joosten
Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA.|Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Ramnik J
RJ
Xavier
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Jos W M
JWM
van der Meer
Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands.
Hendrik G
HG
Stunnenberg
Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
Mihai G
MG
Netea
D000818:Animals; D002176:Candida albicans / Q000276:immunology* / Q000502:physiology; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000276:immunology; D000099181:Dectin-1
D016207:Cytokines; D037181:Lectins, C-Type; D019908:Proto-Oncogene Proteins c-raf; D000099181:Dectin-1