TY  - JOUR
AU  - Eissing, M.L.L.G.
AU  - Ripken, L.S.
AU  - Schreibelt, G.
AU  - Westdorp, H.
AU  - Ligtenberg, M.J.
AU  - Netea-Maier, R.T.
AU  - Netea, M.G.
AU  - Vries, I.J.M. de
AU  - Hoogerbrugge, N.
PY  - 2018
UR  - https://hdl.handle.net/2066/200303
AB  - Carriers of a pathogenic germline mutations in the PTEN gene, a well-known tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, e.g. breast, thyroid, endometrial and colon cancer. This is called PTEN Hamartomous Tumor Syndrome (PHTS). PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. The effects of PTEN on the immune system have been studied in murine knockout models demonstrating that loss of PTEN function leads to dysregulation of the immune response. This results in susceptibility to autoimmunity, impaired B cell class switching with subsequent hypogammaglobulinemia. Additionally, a decreased ability of dendritic cells to prime CD8(+) T cells was observed, leading to impaired tumor eradication. Immune dysfunction in PHTS patients has not yet been extensively studied but might be a manageable contributing factor to the increased cancer risk in PHTS.
TI  - PTEN Hamartoma Tumor Syndrome and Immune Dysregulation
EP  - 367
SN  - 1936-5233
IS  - iss. 2
SP  - 361
JF  - Translational Oncology
VL  - vol. 12
DO  - https://doi.org/10.1016/j.tranon.2018.11.003
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/200303/200303.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Lachmandas, E.L.
AU  - Thiem, K.
AU  - Heuvel, C.N.A.M. van den
AU  - Hijmans, A.G.M.
AU  - Galan, B.E. de
AU  - Tack, C.J.
AU  - Netea, M.G.
AU  - Crevel, R. van
AU  - Diepen, J.A. van
PY  - 2018
UR  - https://hdl.handle.net/2066/183988
TI  - Patients with type 1 diabetes mellitus have impaired IL-1 beta production in response to Mycobacterium tuberculosis
EP  - 380
SN  - 0934-9723
IS  - iss. 2
SP  - 371
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 37
DO  - https://doi.org/10.1007/s10096-017-3145-y
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/183988/183988.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Plantinga, T.S.
AU  - Arts, P.
AU  - Knarren, G.H.
AU  - Mulder, A.H.
AU  - Wakelkamp, I.M.
AU  - Hermus, A.R.M.M.
AU  - Joosten, L.A.
AU  - Netea, M.G.
AU  - Gilissen, C.F.
AU  - Veltman, J.A.
AU  - Hoischen, A.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
PY  - 2017
UR  - https://hdl.handle.net/2066/179606
TI  - Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease
EP  - 1024
SN  - 0009-9236
IS  - iss. 6
SP  - 1017
JF  - Clinical Pharmacology and Therapeutics
VL  - vol. 102
DO  - https://doi.org/10.1002/cpt.733
ER  - 
TY  - JOUR
AU  - Tesselaar, M.H.
AU  - Crezee, T.
AU  - Swarts, H.G.
AU  - Gerrits, D.
AU  - Boerman, O.C.
AU  - Koenderink, J.B.
AU  - Stunnenberg, H.
AU  - Netea, M.G.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
PY  - 2017
UR  - https://hdl.handle.net/2066/165740
AB  - Up to 20%-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy-activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in thyroid cancer cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and FOS activation. Cell proliferation was inhibited by downregulating AKT1 and by induction of autophagy and p21-dependent cell-cycle arrest. Digitalis-like compounds, also designated as cardiac glycosides for their well-characterized beneficial effects in the treatment of heart disease, could therefore represent a promising repositioned treatment modality for patients with RAI-refractory thyroid carcinoma. Mol Cancer Ther; 16(1); 169-81. (c)2016 AACR.
TI  - Digitalis-like Compounds Facilitate Non-Medullary Thyroid Cancer Redifferentiation through Intracellular Ca2+, FOS, and Autophagy-Dependent Pathways
EP  - 181
SN  - 1535-7163
IS  - iss. 1
SP  - 169
JF  - Molecular Cancer Therapeutics
VL  - vol. 16
PS  - 13 p.
DO  - https://doi.org/10.1158/1535-7163.MCT-16-0460
ER  - 
TY  - JOUR
AU  - Becker, K.L.
AU  - Arts, P.
AU  - Jaeger, M.
AU  - Plantinga, T.S.
AU  - Gilissen, C.F.
AU  - Laarhoven, A. van
AU  - Ingen, J. van
AU  - Veltman, J.A.
AU  - Joosten, L.A.B.
AU  - Hoischen, A.
AU  - Netea, M.G.
AU  - Iseman, M.D.
AU  - Chan, E.D.
AU  - Veerdonk, F.L. van de
PY  - 2017
UR  - https://hdl.handle.net/2066/169740
TI  - MST1R mutation as a genetic cause of Lady Windermere syndrome
SN  - 0903-1936
IS  - iss. 1
JF  - European Respiratory Journal
VL  - vol. 49
DO  - https://doi.org/10.1183/13993003.01478-2016
ER  - 
TY  - JOUR
AU  - Ifrim, D.C.
AU  - Quintin, J.
AU  - Courjol, F.
AU  - Verschueren, I.
AU  - Krieken, J.H.J.M. van
AU  - Koentgen, F.
AU  - Fradin, C.
AU  - Gow, N.A.
AU  - Joosten, L.A.B.
AU  - Meer, J.W.M. van der
AU  - Veerdonk, F.L. van de
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/171684
AB  - Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naive wild-type and Dectin-2(-/-) mice, apart from the beta-mannan-deficient bmt1Delta/bmt2Delta/bmt5Delta triple mutant, suggesting that beta-mannan may partially mask alpha-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.
TI  - The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis
EP  - 276
SN  - 1079-9907
IS  - iss. 4
SP  - 267
JF  - Journal of Interferon and Cytokine Research
VL  - vol. 36
DO  - http://dx.doi.org/10.1089/jir.2015.0040
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171684/171684.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Arts, R.W.
AU  - Plantinga, T.S.
AU  - Tuit, S.
AU  - Ulas, T.
AU  - Heinhuis, B.
AU  - Tesselaar, M.
AU  - Sloot, Y.
AU  - Adema, G.J.
AU  - Joosten, L.A.B.
AU  - Smit, J.W.A.
AU  - Netea, M.G.
AU  - Netea, R.T.
PY  - 2016
UR  - https://hdl.handle.net/2066/171836
TI  - Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages.
SN  - 2162-4011
IS  - iss. 12
SP  - e1229725
JF  - Oncoimmunology
VL  - vol. 5
DO  - https://doi.org/10.1080/2162402X.2016.1229725
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171836/171836.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Vogelaar, I.P.
AU  - Ligtenberg, M.J.
AU  - Post, R.S. van der
AU  - Voer, R.M. de
AU  - Kets, C.M.
AU  - Jansen, T.J.
AU  - Jacobs, L.
AU  - Schreibelt, G.
AU  - Vries, I.J. de
AU  - Netea, M.G.
AU  - Hoogerbrugge, N.
PY  - 2016
UR  - https://hdl.handle.net/2066/171354
AB  - Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.
TI  - Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect
EP  - 296
SN  - 1389-9600
IS  - iss. 2
SP  - 289
JF  - Familial Cancer
VL  - vol. 15
DO  - https://doi.org/10.1007/s10689-015-9859-z
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171354/171354.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Jaeger, M.
AU  - Carvalho, A.
AU  - Cunha, C.
AU  - Plantinga, T.S.
AU  - Veerdonk, F.L. van de
AU  - Puccetti, M.
AU  - Galosi, C.
AU  - Joosten, L.A.B.
AU  - DuPont, B.
AU  - Kullberg, B.J.
AU  - Sobel, J.D.
AU  - Romani, L.
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/171893
AB  - Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1beta and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1beta production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1beta-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease.
TI  - Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC
EP  - 801
SN  - 0934-9723
IS  - iss. 5
SP  - 797
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 35
DO  - https://doi.org/10.1007/s10096-016-2600-5
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171893/171893.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Heinhuis, B.
AU  - Plantinga, T.S.
AU  - Semango, G.
AU  - Kusters, B.
AU  - Netea, M.G.
AU  - Dinarello, C.A.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Joosten, L.A.B.
PY  - 2016
UR  - https://hdl.handle.net/2066/168061
AB  - Alternative splicing is a biological mechanism that enables the synthesis of several isoforms with different or even opposite functions. This process must be tightly regulated to prevent unwanted isoform expression favoring pathological processes. Some isoforms of interleukin 32 (IL-32) are reported to be more potent in inducing inflammation, however the role in cell death remains to be investigated. This study demonstrates that IL-32gamma and IL-32beta can induce caspase-8-dependent cell death whereas this was not observed for IL-32alpha. Overexpression of IL-32beta or IL-32gamma but not IL-32alpha, resulted in enhanced expression of the survival cytokine IL-8. Furthermore, restoring the IL-8 signaling pathway by overexpressing CXCR1 in HEK293 cells, rescued IL-32beta but not IL-32gamma-induced cell death. Interestingly, IL-32gamma was able to downregulate CXCR1 and thereby induce cell death. Subsequent studies into the role of IL-32 in thyroid cancer (TC) revealed that several IL-32 isoforms, IL-8, and CXCR1 are expressed in TC cell lines and specimens. Remarkably, TC cell lines were found to produce high concentrations of IL-8, indicating an important role for IL-8 in the survival-signaling pathway in these cells. Intriguingly, a significant correlation between the IL-8 receptor CXCR1 and IL-32gamma was observed in TC specimens, while this was not observed for the other IL-32 splice variants. Blocking IL-32 alternative splicing by Isoginkgetin resulted in predominant expression of IL-32gamma splice variants and cell death in TC cell lines. All together, modulation of IL-32 alternative splicing could represent a novel strategy for the treatment of malignancies, in particular thyroid cancer.
TI  - Alternatively spliced isoforms of IL-32 differentially influence cell death pathways in cancer cell lines
EP  - 205
SN  - 0143-3334
IS  - iss. 2
SP  - 197
JF  - Carcinogenesis
VL  - vol. 37
DO  - https://doi.org/10.1093/carcin/bgv172
ER  - 
TY  - JOUR
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
AU  - Veerdonk, F.L. van de
AU  - Smit, J.W.A.
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/170985
AB  - Autophagy and inflammation are 2 fundamental biological processes involved in both physiological and pathological conditions. Through its crucial role in maintaining cellular homeostasis, autophagy is involved in modulation of cell metabolism, cell survival, and host defense. Defective autophagy is associated with pathological conditions such as cancer, autoimmune disease, neurodegenerative disease, and senescence. Inflammation represents a crucial line of defense against microorganisms and other pathogens, and there is increasing evidence that autophagy has important effects on the induction and modulation of the inflammatory reaction; understanding the balance between these 2 processes may point to important possibilities for therapeutic targeting. This review focuses on the crosstalk between autophagy and inflammation as an emerging field with major implications for understanding the host defense on the one hand, and for the pathogenesis and treatment of immune-mediated diseases on the other hand.
TI  - Modulation of inflammation by autophagy: Consequences for human disease
EP  - 260
SN  - 1554-8627
IS  - iss. 2
SP  - 245
JF  - Autophagy
VL  - vol. 12
DO  - https://doi.org/10.1080/15548627.2015.1071759
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/170985/170985.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Lachmandas, E.L.
AU  - Heuvel, C.N.A.M. van den
AU  - Damen, M.S.M.A.
AU  - Cleophas, M.C.P.
AU  - Netea, M.G.
AU  - Crevel, R. van
PY  - 2016
UR  - https://hdl.handle.net/2066/172304
AB  - Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.
TI  - Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids
SN  - 2314-6745
SP  - 6014631
JF  - Journal of Diabetes Research
VL  - vol. 2016
DO  - https://doi.org/10.1155/2016/6014631
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/172304/172304.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Wilson, G.J.
AU  - Marakalala, M.J.
AU  - Hoving, J.C.
AU  - van Laarhoven, A.
AU  - Drummond, R.A.
AU  - Kerscher, B.
AU  - Keeton, R.
AU  - van de Vosse, E.
AU  - Ottenhoff, T.H.
AU  - Plantinga, T.S.
AU  - Alisjahbana, B.
AU  - Govender, D.
AU  - Besra, G.S.
AU  - Netea, M.G.
AU  - Reid, D.M.
AU  - Willment, J.A.
AU  - Jacobs, M.
AU  - Yamasaki, S.
AU  - Crevel, R. van
AU  - Brown, G.D.
PY  - 2015
UR  - https://hdl.handle.net/2066/154103
AB  - The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8-/- mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8-/- mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man.
TI  - The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity
EP  - 259
SN  - 1931-3128
IS  - iss. 2
SP  - 252
JF  - Cell Host & Microbe
VL  - vol. 17
DO  - https://doi.org/10.1016/j.chom.2015.01.004
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/154103/154103.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Jaeger, M.
AU  - Lee, R.T.J.G. van der
AU  - Cheng, S.C.
AU  - Johnson, M.D.
AU  - Kumar, V.
AU  - Ng, A.
AU  - Plantinga, T.S.
AU  - Smeekens, S.P.
AU  - Oosting, M.
AU  - Wang, X.
AU  - Barchet, W.
AU  - Fitzgerald, K.
AU  - Joosten, L.A.B.
AU  - Perfect, J.R.
AU  - Wijmenga, C.
AU  - Veerdonk, F.L. van de
AU  - Huijnen, M.A.
AU  - Xavier, R.J.
AU  - Kullberg, B.J.
AU  - Netea, M.G.
PY  - 2015
UR  - https://hdl.handle.net/2066/154134
AB  - The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In this study, we present complementary evidence based on transcriptome analysis, genetics, and immunological studies in knockout mice and humans that the cytosolic RIG-I-like receptor MDA5 (IFIH1) has an important role in the host defense against C. albicans. Firstly, IFIH1 expression in macrophages is specifically induced by invasive C. albicans hyphae, and patients suffering from chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy controls. Secondly, there is a strong association between missense variants in the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida infections. Thirdly, cells from Mda5 knockout mice and human peripheral blood mononuclear cells (PBMCs) with different IFIH1 genotypes display an altered cytokine response to C. albicans. These data strongly suggest that MDA5 is involved in immune responses to Candida infection. As a receptor for viral RNA, MDA5 until now has been linked to antiviral host defense, but these novel studies show unexpected effects in antifungal immunity as well. Future studies are warranted to explore the potential of MDA5 as a novel target for immunotherapeutic strategies.
TI  - The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections
EP  - 974
SN  - 0934-9723
IS  - iss. 5
SP  - 963
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 34
DO  - https://doi.org/10.1007/s10096-014-2309-2
ER  - 
TY  - JOUR
AU  - Ifrim, D.C.
AU  - Bain, J.M.
AU  - Reid, D.M.
AU  - Oosting, M.
AU  - Verschueren, I.
AU  - Gow, N.A.
AU  - Krieken, J.H.J.M. van
AU  - Brown, G.D.
AU  - Kullberg, B.J.
AU  - Joosten, L.A.B.
AU  - Meer, J.W.M. van der
AU  - Koentgen, F.
AU  - Erwig, L.P.
AU  - Quintin, J.
AU  - Netea, M.G.
PY  - 2014
UR  - https://hdl.handle.net/2066/136746
AB  - Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here, we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2(-/-) mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate yet significant decrease in phagocytosis of the fungus by the Dectin-2(-/-) macrophages and neutrophils. Neutrophils of Dectin-2(-/-) mice also displayed lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights into the host defense mechanisms against this important fungal pathogen.
TI  - Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata
EP  - 1073
SN  - 0019-9567
IS  - iss. 3
SP  - 1064
JF  - Infection and Immunity
VL  - vol. 82
DO  - https://doi.org/10.1128/IAI.01189-13
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/136746/136746.pdf?sequence=1
ER  -