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1. Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients

Author

Cordonnier, Catherine, Cesaro, Simone, Maschmeyer, Georg, Einsele, Hermann, Peter Donnelly, J., Alanio, Alexandre, Hauser, Philippe M., Lagrou, Katrien, Melchers, Willem J. G., Helweg-Larsen, Jannik, Matos, Olga, Bretagne, Stephane, Maertens, Johan, Agrawal, Samir, Kibbler, Christopher, Pagliuca, Antonio, Ward, Katherine, Akova, Murat, Herbrecht, Raoul, Mallet, Vincent, Ribaud, Patricia, Aljurf, Mahmoud, Averbuch, Dina, Engelhard, Dan, Berg, Thomas, Cornely, Oliver, Penack, Olaf, van Boemmel, Florian, von Lilienfeld-Toal, Marie, Blennow, Ola, Ljungman, Per, Bruggemann, Roger, Donnelly, Peter, Kullberg, Bart-Jan, Melchers, Willem, Calandra, Thierry, Hirsch, Hans, Marchetti, Oscar, Orasch, Christina, Tissot, Frederic, Castagnola, Elio, Girmenia, Corrado, Mikulska, Malgorzata, Pagano, Livio, Viscoli, Claudio, De La Camara, Rafael, Duarte, Rafael, Munoz, Patricia, Drgona, Lubos, Hargreaves, Ruth, Hubacek, Petr, Kouba, Michal, Racil, Zdenek, Klyasova, Galina, Pettrikos, George, Roilides, Emmanuel, Skiada, Anna, Rizzi-Puechal, Valã©rie, Sinko, Janos, Slavin, Monica, Styczynski, Jan, Tweddle, Lorraine, Wood, Craig, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Haematology, Oncoematologia Pediatrica, Policlinico G. B. Rossi, Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Radboud university [Nijmegen], Université Sorbonne Paris Cité (USPC), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Lausanne University Hospital, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Department of Hematology, University Hospital Gasthuisberg, The ECIL-5 meeting was supported by unrestricted educational grants from Astellas Pharma, Gilead Sciences, Merck, and Pfizer. The ECIL-6 meeting was supported by unrestricted educational grants from Basilea, Gilead Sciences, Merck, and Pfizer, on behalf of the Fifth European Conference on Infections in Leukemia (ECIL-5†), a joint venture of The European Group for Blood and Marrow Transplantation (EBMT), The European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and The European Leukemia Net (ELN) (61 collabrators), Radboud University [Nijmegen], University Hospital Gasthuisberg [Leuven], Julius-Maximilians-Universität Würzburg (JMU), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Antifungal Agents, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Disease, Hematopoietic stem cell transplantation, Pneumocystis carinii, Chemoprevention, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Pneumocystis jirovecii, Pharmacology (medical), Intensive care medicine, Hematologic Neoplasms, Pneumonia, Pneumocystis, Stem Cell Transplantation, Transplant Recipients, Pharmacology, Infectious Diseases, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Hematology, biology, Pneumocystis, business.industry, Mortality rate, Pneumonia, biology.organism_classification, medicine.disease, Penumocytis pneumonia, 3. Good health, Leukemia, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030220 oncology & carcinogenesis, immunocomrpomised host, Pnemocystis jirovecii, Stem cell, immunocomrpomised host, Penumocytis pneumonia, Pnemocystis jirovecii, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 171209.pdf (Publisher’s version ) (Closed access) Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%-60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors.

Published
2016

2. Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients-authors' response

Author

Cordonnier, Catherine, Alanio, Alexandre, Cesaro, Simone, Maschmeyer, Georg, Einsele, Hermann, Donnelly, J. Peter, Hauser, Philippe M., Lagrou, Katrien, Melchers, Willem J. G., Helweg-Larsen, Jannik, Matos, Olga, Bretagne, Stéphane, Maertens, Johan, Agrawal, Samir, Akova, Murat, Aljurf, Mahmoud, Averbuch, Dina, Berg, Thomas, Blennow, Ola, Brüggemann, Roger, Calandra, Thierry, Castagnola, Elio, Cornely, Oliver, De La Camara, Rafael, Drgona, Lubos, Duarte, Rafael, Engelhard, Dan, Girmenia, Corrado, Hargreaves, Ruth, Herbrecht, Raoul, Hirsch, Hans, Hubacek, Petr, Kibbler, Christopher, Klyasova, Galina, Kouba, Michal, Kullberg, Bart-Jan, Ljungman, Per, Mallet, Vincent, Marchetti, Oscar, Mikulska, Malgorzata, Munoz, Patricia, Orasch, Christina, Pagano, Livio, Pagliuca, Antonio, Penack, Olaf, Pettrikos, George, Racil, Zdenek, Ribaud, Patricia, Rizzi-Puechal, Valérie, Roilides, Emmanuel, Sinko, Janos, Skiada, Anna, Slavin, Monica, Styczynski, Jan, Tissot, Frederic, Tweddle, Lorraine, van Boemmel, Florian, von Lilienfeld-Toal, Marie, Viscoli, Claudio, Ward, Katherine, and Wood, Craig

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, HIV Infections, Pneumocystis carinii, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Hematologic Neoplasms, Humans, Pneumonia, Pneumocystis, Stem Cell Transplantation, Pharmacology, Pharmacology (medical), Infectious Diseases, Medicine, In patient, Intensive care medicine, hematopoietic stem cell transplant, business.industry, Pneumocystis, PNEUMOCYSTIS JIROVECI, Pneumocystis jiroveci, infection, hematopoietic stem cell transplant, Pneumocystis jirovecii Pneumonia, Pneumocystis jiroveci, Pneumonia, medicine.disease, infection, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Stem cell, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 169784.pdf (Publisher’s version ) (Closed access)

Published
2017

3. AIDS-related mycoses: the way forward

Author

Brown, Gordon D, Meintjes, Graeme, Kolls, Jay K, Gray, Clive, Horsnell, William, Working Group from the EMBO-AIDS Related Mycoses Workshop, Achan, Beatrice, Alber, Gottfried, Aloisi, Maria, Armstrong-James, Darius, Beale, Mathew, Bicanic, Tihana, Black, John, Bohjanen, Paul, Botes, Angela, Boulware, David R, Brown, Gordon, Bunjun, Rubina, Carr, William, Casadevall, Arturo, Chang, Christina, Chivero, Ernest, Corcoran, Craig, Cross, Anna, Dawood, Halima, Day, Jeremy, De Bernardis, Flavia, De Jager, Veronique, De Repentigny, Louis, Denning, David, Eschke, Maria, Finkelman, Malcolm, Govender, Nelesh, Gow, Neil, Graham, Lisa, Gryschek, Ronaldo, Hammond-Aryee, Kenneth, Harrison, Tom, Heard, Neil, Hill, Melanie, Hoving, J Claire, Janoff, Edward, Jarvis, Joseph, Kayuni, Sekeleghe, King, Karin, Kolls, Jay, Kullberg, Bart-Jan, Lalloo, David G, Letang, Emilio, Levitz, Stuart, Limper, Andrew, Longley, Nicky, Machiridza, Tendai Rodney, Mahabeer, Yesholata, Martinsons, Neil, Meiring, Susan, Meya, David, Miller, Robert, Molloy, Sile, Morris, Lynn, Mukaremera, Liliane, Musubire, Abdu K, Muzoora, Conrad, Nair, Amy, Nakiwala Kimbowa, Justine, Netea, Mihai, Nielsen, Kirsten, O'hern, Jennifer, Okurut, Samuel, Parker, Arifa, Patterson, Tom, Pennap, Grace, Perfect, John, Prinsloo, Chrisna, Rhein, Joshua, Rolfes, Melissa A, Samuel, Catherine, Schutz, Charlotte, Scriven, James, Sebolai, Olihile M, Sojane, Katlego, Sriruttan, Charlotte, Stead, David, Steyn, Annica, Thawer, Narjis K, Thienemann, Friedrich, Von Hohenberg, Maximilian, Vreulink, Jo-marie, Wessels, Jeannette, Wood, Kathryn, and Yang, Yun-liang

Subjects
Microbiology (medical), medicine.medical_specialty, Medical mycology, AIDS-Related Opportunistic Infections, Human immunodeficiency virus (HIV), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Developing country, Translational research, Biology, medicine.disease_cause, medicine.disease, Microbiology, Article, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Acquired immunodeficiency syndrome (AIDS), Virology, Immunology, Epidemiological surveillance, medicine, Intensive care medicine
Abstract

Item does not contain fulltext The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.

Published
2014

4. Immunologic defects in severe mucocutaneous HSV-2 infections: Response to IFN-gamma therapy

Author

Joris A. Veltman, Alexander Hoischen, Frank J. M. van Kuppeveld, Martijn A. Huynen, Jos W. M. van der Meer, Peer Arts, Bart Jan Kullberg, Christian Gilissen, Martijn A. Langereis, Wendy A. G. van Zelst-Stams, Robin van der Lee, Frank L. van de Veerdonk, Mihai G. Netea, Arts, Peer, Van De Veerdonk, Frank L, van der Lee, Robin, Langereis, Martijn A, Gilissen, Christian, van Zelst-Stams, Wendy A G, Huynen, Martijn A, van der Meer, Jos W M, van Kuppeveld, Frank J, Veltman, Joris A, Kullberg, Bart Jan, Hoischen, Alexander, Netea, Mihai G, Genetica & Celbiologie, Klinische Genetica, and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Immunology, Mucocutaneous zone, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HSL and HSV, immune response, law.invention, 03 medical and health sciences, 0302 clinical medicine, Text mining, law, medicine, Immunology and Allergy, Interferon gamma, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], 030104 developmental biology, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030220 oncology & carcinogenesis, Recombinant DNA, business, herpes simplex virus 2, medicine.drug, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 167300.pdf (Publisher’s version ) (Closed access)

Published
2016

5. Human TLR10 is an anti-inflammatory pattern-recognition receptor

Author

Gosse J. Adema, Mihai G. Netea, Ineke Verschueren, Anja Garritsen, Shih-Chin Cheng, Peer Arts, Leo A. B. Joosten, Theo S. Plantinga, Patrick D. J. Sturm, Judith M. Bolscher, Bart Jan Kullberg, Marije Oosting, Jos W. M. van der Meer, Alexander Hoischen, Rachel Vestering-Stenger, Hans van Eenennaam, Oosting, Marije, Cheng, Shih Chin, Bolscher, Judith M, Vestering-Stenger, Rachel, Plantinga, Theo S, Verschueren, Ineke C, Arts, Peer, Garritsen, Anja, Van Eenennaam, Hans, Sturm, Patrick, Kullberg, Bart Jan, Hoischen, Alexander, Adema, Gosse J, Van Der Meer, Jos WM, Netea, Mihai G, and Joosten, Leo AB

Subjects
Male, medicine.drug_class, medicine.medical_treatment, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Interleukin-1beta, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Mice, Transgenic, Biology, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Polymorphism, Single Nucleotide, Proinflammatory cytokine, immunology, Mice, medicine, Animals, Humans, Receptor, Inflammation, TLR10, Multidisciplinary, Polymorphism, Genetic, Interleukin-6, Tumor Necrosis Factor-alpha, Receptor antagonist, Molecular biology, cytokines, Toll-Like Receptor 2, Up-Regulation, Mice, Inbred C57BL, TLR2, Interleukin 10, Interleukin 1 Receptor Antagonist Protein, Cytokine, HEK293 Cells, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], PNAS Plus, Interleukin-21 receptor, Receptors, Pattern Recognition, Toll-Like Receptor 10, Leukocytes, Mononuclear, Cytokines, RNA Interference, Signal transduction, Neurodevelopmental disorders Radboud Institute for Molecular Life Sciences [Radboudumc 7], SNPs, Signal Transduction
Abstract

Item does not contain fulltext Toll-like receptor (TLR) 10 is the only pattern-recognition receptor without known ligand specificity and biological function. We demonstrate that TLR10 is a modulatory receptor with mainly inhibitory effects. Blocking TLR10 by antagonistic antibodies enhanced proinflammatory cytokine production, including IL-1 beta, specifically after exposure to TLR2 ligands. Blocking TLR10 after stimulation of peripheral blood mononuclear cells with pam3CSK4 (Pam3Cys) led to production of 2,065 +/- 106 pg/mL IL-1 beta (mean +/- SEM) in comparison with 1,043 +/- 51 pg/mL IL-1 beta after addition of nonspecific IgG antibodies. Several mechanisms mediate the modulatory effects of TLR10: on the one hand, cotransfection in human cell lines showed that TLR10 acts as an inhibitory receptor when forming heterodimers with TLR2; on the other hand, cross-linking experiments showed specific induction of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra, 16 +/- 1.7 ng/mL, mean +/- SEM). After cross-linking anti-TLR10 antibody, no production of IL-1 beta and other proinflammatory cytokines could be found. Furthermore, individuals bearing TLR10 polymorphisms displayed an increased capacity to produce IL-1 beta, TNF-alpha, and IL-6 upon ligation of TLR2, in a gene-dose-dependent manner. The modulatory effects of TLR10 are complex, involving at least several mechanisms: there is competition for ligands or for the formation of heterodimer receptors with TLR2, as well as PI3K/Akt-mediated induction of the anti-inflammatory cytokine IL-1Ra. Finally, transgenic mice expressing human TLR10 produced fewer cytokines when challenged with a TLR2 agonist. In conclusion, to our knowledge we demonstrate for the first time that TLR10 is a modulatory pattern-recognition receptor with mainly inhibitory properties.

Published
2014

6. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis

Author

Alexander Hoischen, Mihai G. Netea, Diana C. Rosentul, Bart Jan Kullberg, Desa Lilic, Frank L. van de Veerdonk, Christian Gilissen, Chantal A.A. Smits-van der Graaf, Theo S. Plantinga, Leo A. B. Joosten, Andrew J. Carmichael, Joris A. Veltman, Peer Arts, Sanne P. Smeekens, Jos W. M. van der Meer, Van De Veerdonk, Frank L, Plantinga, Theo S, Hoischen, Alexander, Smeekens, Sanne P, Joosten, Leo AB, Gilissen, Christian, Arts, Peer, Rosentul, Diana C, Carmichael, Andrew J, Smits-van Der Graaf, Chantal AA, Kullberg, Bart Jan, Van Der Meer, Jos WM, Lilic, Desa, Veltman, Joris A, and Netea, Mihai G

Subjects
Mucocutaneous zone, Mutation, Missense, Biology, medicine.disease_cause, Invasive mycoses and compromised host Infection and autoimmunity [N4i 2], Autoimmunity, Chronic mucocutaneous candidiasis, Interferon-gamma, CMC, medicine, Humans, Missense mutation, Gene, Mutation, Stat1 gene, Autosome, Interleukins, Candidiasis, Chronic Mucocutaneous, Interleukin-17, Sequence Analysis, DNA, General Medicine, Th1 Cells, medicine.disease, Autoimmune regulator, Protein Structure, Tertiary, Pathogenesis and modulation of inflammation [N4i 1], STAT1 Transcription Factor, Haplotypes, Immunology, Th17 Cells, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], Poverty-related infectious diseases Aetiology, screening and detection [N4i 3], Signal Transduction
Abstract

Contains fulltext : 98330.pdf (Publisher’s version ) (Closed access) BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to candida infection of skin, nails, and mucous membranes. Patients with recessive CMC and autoimmunity have mutations in the autoimmune regulator AIRE. The cause of autosomal dominant CMC is unknown. METHODS: We evaluated 14 patients from five families with autosomal dominant CMC. We incubated their peripheral-blood mononuclear cells with different combinations of stimuli to test the integrity of pathways that mediate immunity, which led to the selection of 100 genes that were most likely to contain the genetic defect. We used an array-based sequence-capture assay, followed by next-generation sequencing, to identify mutations. RESULTS: The mononuclear cells from the affected patients were characterized by poor production of interferon-gamma, interleukin-17, and interleukin-22, suggesting that the defect lay within the interleukin-12 receptor and interleukin-23 receptor signaling pathways. We identified heterozygous missense mutations in the DNA sequence encoding the coiled-coil (CC) domain of signal transducer and activator of transcription 1 (STAT1) in the patients. These mutations lead to defective responses in type 1 and type 17 helper T cells (Th1 and Th17). The interferon-gamma receptor pathway was intact in these patients. CONCLUSIONS: Mutations in the CC domain of STAT1 underlie autosomal dominant CMC and lead to defective Th1 and Th17 responses, which may explain the increased susceptibility to fungal infection. (Funded by the Netherlands Organization for Scientific Research and others.).

Published
2011

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