Host and Environmental Factors Influencing Individual Human Cytokine Responses.
Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies. PAPERCLIP.
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Rob
R
Ter Horst
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Martin
M
Jaeger
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Sanne P
SP
Smeekens
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Marije
M
Oosting
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Groningen 9700RB, the Netherlands.
Morris A
MA
Swertz
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Groningen 9700RB, the Netherlands.
Yang
Y
Li
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Groningen 9700RB, the Netherlands.
Vinod
V
Kumar
Laboratory of Pediatric Infectious Diseases and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Dimitri A
DA
Diavatopoulos
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Anne F M
AFM
Jansen
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Heidi
H
Lemmers
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Helga
H
Toenhake-Dijkstra
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Antonius E
AE
van Herwaarden
Department of Rheumatology, Rijnstate Hospital, Arnhem, Gelderland 6815AD, the Netherlands.
Matthijs
M
Janssen
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Renate G
RG
van der Molen
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Irma
I
Joosten
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Fred C G J
FCGJ
Sweep
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands; Division of Endocrinology, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Johannes W
JW
Smit
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands; Division of Endocrinology, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Romana T
RT
Netea-Maier
Elkerliek Hospital, Clinical Chemistry, Helmond, Noord-Brabant 5700AB, the Netherlands.
Mieke M J F
MMJF
Koenders
Broad Institute of Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA; Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02139, USA.
Ramnik J
RJ
Xavier
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Jos W M
JWM
van der Meer
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands; Division of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Charles A
CA
Dinarello
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
Norman
N
Pavelka
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Groningen 9700RB, the Netherlands; Centre for Immune Regulation and Department of Immunology, University of Oslo, Oslo University Hospital, Oslo, Oslo 0027, Norway.
Cisca
C
Wijmenga
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands.
Richard A
RA
Notebaart
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands. Electronic address: leo.joosten@radboudumc.nl.
Leo A B
LAB
Joosten
Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands. Electronic address: mihai.netea@radboudumc.nl.
Mihai G
MG
Netea
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D001168:Arthritis / Q000276:immunology; D001769:Blood / Q000276:immunology; D015992:Body Mass Index; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D005260:Female; D059647:Gene-Environment Interaction; D016045:Human Genome Project; D006801:Humans; D007239:Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D012621:Seasons; D012727:Sex Characteristics
D016207:Cytokines
age; alpha-1-antitrypsin; cytokines; environment; gender; genetics; host; microbiome; season; vitamin D