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Article ; Online: Transmembrane protein 14A protects glomerular filtration barrier integrity.

Khalil, Ramzi / Bonnemaijer, Josephine D D / Kreutz, Reinhold / Spaink, Herman P / Hogendoorn, Pancras C W / Baelde, Hans J

Physiological reports

2023 Volume 11, Issue 23, Page(s) e15847

Abstract: Transmembrane protein 14A (TMEM14A) is a relatively unknown protein that is now identified to be required for maintaining the integrity of the glomerular filtration barrier. It is an integral transmembrane protein of 99 amino acids with three ... ...

Abstract	Transmembrane protein 14A (TMEM14A) is a relatively unknown protein that is now identified to be required for maintaining the integrity of the glomerular filtration barrier. It is an integral transmembrane protein of 99 amino acids with three transmembrane domains. TMEM14A has been implied to suppress Bax-mediated apoptosis in other studies. Other than that, little is currently known of its function. Here, we show that its expression is diminished before onset of proteinuria in a spontaneously proteinuric rat model. Knocking down tmem14a mRNA translation results in proteinuria in zebrafish embryos without affecting tubular reabsorption. Also, it is primarily expressed by podocytes. Lastly, an increase in glomerular TMEM14A expression is exhibited in various proteinuric renal diseases. Overall, these results suggest that TMEM14A is a novel factor in the protective mechanisms of the nephron to maintain glomerular filtration barrier integrity.
MeSH term(s)	Animals ; Rats ; Glomerular Filtration Barrier ; Kidney Glomerulus/metabolism ; Podocytes/metabolism ; Proteinuria/metabolism ; Zebrafish/genetics ; Zebrafish/metabolism ; Membrane Proteins/genetics ; Apoptosis Regulatory Proteins/genetics
Chemical Substances	Membrane Proteins ; Apoptosis Regulatory Proteins
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15847
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Immunological factors linked to geographical variation in vaccine responses.

van Dorst, Marloes M A R / Pyuza, Jeremia J / Nkurunungi, Gyaviira / Kullaya, Vesla I / Smits, Hermelijn H / Hogendoorn, Pancras C W / Wammes, Linda J / Everts, Bart / Elliott, Alison M / Jochems, Simon P / Yazdanbakhsh, Maria

Nature reviews. Immunology

2023 Volume 24, Issue 4, Page(s) 250–263

Abstract: Vaccination is one of medicine's greatest achievements; however, its full potential is hampered by considerable variation in efficacy across populations and geographical regions. For example, attenuated malaria vaccines in high-income countries confer ... ...

Abstract	Vaccination is one of medicine's greatest achievements; however, its full potential is hampered by considerable variation in efficacy across populations and geographical regions. For example, attenuated malaria vaccines in high-income countries confer almost 100% protection, whereas in low-income regions these same vaccines achieve only 20-50% protection. This trend is also observed for other vaccines, such as bacillus Calmette-Guérin (BCG), rotavirus and yellow fever vaccines, in terms of either immunogenicity or efficacy. Multiple environmental factors affect vaccine responses, including pathogen exposure, microbiota composition and dietary nutrients. However, there has been variable success with interventions that target these individual factors, highlighting the need for a better understanding of their downstream immunological mechanisms to develop new ways of modulating vaccine responses. Here, we review the immunological factors that underlie geographical variation in vaccine responses. Through the identification of causal pathways that link environmental influences to vaccine responsiveness, it might become possible to devise modulatory compounds that can complement vaccines for better outcomes in regions where they are needed most.
MeSH term(s)	Humans ; BCG Vaccine ; Vaccination ; Immunologic Factors ; Vaccines, Attenuated
Chemical Substances	BCG Vaccine ; Immunologic Factors ; Vaccines, Attenuated
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-023-00941-2
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Thromboembolic involvement and its possible pathogenesis in COVID-19 mortality: lesson from post-mortem reports.

Dwiputra Hernugrahanto, K / Novembri Utomo, D / Hariman, H / Budhiparama, N C / Medika Hertanto, D / Santoso, D / Hogendoorn, P C W

European review for medical and pharmacological sciences

2021 Volume 25, Issue 3, Page(s) 1670–1679

Abstract: The emergence of Coronavirus Disease 19 (COVID-19) as a pandemic has claimed hundreds of thousands of lives worldwide since its initial breakout. With increasing reports from clinical observations and autopsy findings, it became clear that the disease ... ...

Abstract	The emergence of Coronavirus Disease 19 (COVID-19) as a pandemic has claimed hundreds of thousands of lives worldwide since its initial breakout. With increasing reports from clinical observations and autopsy findings, it became clear that the disease causes acute respiratory distress syndrome (ARDS), as well as a broad spectrum of systemic and multiorgan pathologies, including angiopathy, endothelialitis, and thrombosis. Coagulopathy is associated with the activity of megakaryocytes, which play crucial roles in modulating the platelet homeostasis. Only a few autopsy reports include findings on thrombosis formation and the presence of megakaryocytes. Here we review and summarize the possible involvement and the pathophysiology of the thromboembolic events in COVID-19 patients based on post-mortem reports. We reviewed post-mortem reports from March 2020 to September 2020. Eleven autopsy reports that demonstrated thromboembolic involvement findings, either macroscopically or microscopically, were included in this review. All studies reported similar pulmonary gross findings. Not all studies described thrombi formation and megakaryocyte findings. Pulmonary embolism, coagulopathy, severe endothelial injury, and widespread thrombosis are frequent in COVID-19 patients, following many patients with high-level D-Dimer, increased fibrinogen, abnormal prothrombic coagulation, and thrombocytopenia. Reports showed that thrombus was also found in the lower extremities' deep veins and the prostatic venous plexus. In conclusion, a complex interaction of SARS-CoV-2 virus invasion with platelets, leukocytes, endothelial cells, inflammation, immune response, and the possible involvement of megakaryocytes may increase the cumulative risk of thrombosis by a yet unclear cellular and humoral interaction.
MeSH term(s)	Autopsy ; Blood Coagulation ; COVID-19/complications ; COVID-19/mortality ; COVID-19/pathology ; Endothelium, Vascular/pathology ; Humans ; Lung/blood supply ; Lung/pathology ; Megakaryocytes/pathology ; Pandemics ; SARS-CoV-2 ; Thromboembolism/etiology ; Thromboembolism/mortality ; Thromboembolism/pathology
Language	English
Publishing date	2021-02-24
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	605550-3
ISSN	2284-0729 ; 1128-3602 ; 0392-291X
ISSN (online)	2284-0729
ISSN	1128-3602 ; 0392-291X
DOI	10.26355/eurrev_202102_24878
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Zs.A 1887: Show issues

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Article: Conjunctival Leiomyosarcoma, a Rare Neoplasm Always Originating at the Limbus? Report of a New Case and Review of 11 Published Cases.

De Groot, V / Verhelst, E / Hogendoorn, P C W / de Keizer, R J W

Ocular oncology and pathology

2019 Volume 5, Issue 5, Page(s) 333–339

Abstract: Purpose of the study: To describe the differential diagnosis and management of a rare conjunctival malignancy.: Procedures: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor ... ...

Abstract	Purpose of the study: To describe the differential diagnosis and management of a rare conjunctival malignancy. Procedures: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with myogenic differentiation. Six months later, three suspect lesions developed at the border of the previous excision. Pathological diagnosis pointed to a leiomyosarcoma. Adjuvant radiotherapy with strontium-90 brachytherapy was applied. After 3 years, there was neither recurrence nor distant metastases. A literature review revealed 11 cases of conjunctival leiomyosarcoma. Results: All 12 cases seemed to originate at the limbal conjunctiva. Scleral invasion was found only in one patient with multiple previous resections. Corneal invasion was reported in two patients. Four patients had a globe-sparing resection. In two of them, margins were not tumor free and additional brachytherapy gave a tumor-free follow-up of 1 and 3 years. Four cases underwent an exenteration. Conclusion and message: Primary conjunctival leiomyosarcoma is a rare tumor with a favorable prognosis due to early detection and consequently limited size. Diagnosis involves histopathological investigation including immunohistochemistry. If possible, complete resection has the best prognosis. Adjunctive radiotherapy can be effective when the margins are not free and should be considered.
Language	English
Publishing date	2019-01-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2806965-1
ISSN	2296-4657 ; 2296-4681
ISSN (online)	2296-4657
ISSN	2296-4681
DOI	10.1159/000494497
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Article ; Online: Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms.

Kemps, Paul G / Kester, Lennart / Scheijde-Vermeulen, Marijn A / van Noesel, Carel J M / Verdijk, Robert M / Diepstra, Arjan / van Marion, Ariënne M W / Dors, Natasja / van den Bos, Cor / Bruggink, Annette H / Hogendoorn, Pancras C W / van Halteren, Astrid G S

Histopathology

2024 Volume 84, Issue 5, Page(s) 837–846

Abstract: ... in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell ...

Abstract	Aims: The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands. Methods and results: We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist-assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations. Conclusions: This population-based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.
MeSH term(s)	Adult ; Male ; Humans ; Histiocytosis, Langerhans-Cell/epidemiology ; Histiocytosis, Langerhans-Cell/genetics ; Histiocytosis, Langerhans-Cell/pathology ; Histiocytes/pathology ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/pathology ; Dendritic Cells/pathology ; Demography
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15127
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Zs.A 1328: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The incidence, mutational status, risk classification and referral pattern of gastro-intestinal stromal tumours in the Netherlands: a nationwide pathology registry (PALGA) study.

Verschoor, Arie J / Bovée, J V M G / Overbeek, L I H / Hogendoorn, P C W / Gelderblom, H

Virchows Archiv : an international journal of pathology

2018 Volume 472, Issue 2, Page(s) 221–229

Abstract: Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the ... ...

Abstract	Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. From PALGA, the nationwide Dutch Pathology Registry, pathology excerpts from all patients with a GIST or GIST-like tumour between 2003 and 2012 were retrieved to calculate incidence rates. Full pathology reports were retrieved of resections in 2011 and 2012 to study the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. The incidence of GIST increased to 17.7 per million inhabitants in 2012 with a median age of 67 years. Mutational analysis was performed in 33.9% of patients with a resection between 2011 and 2012 (KIT mutation 67.5%, PDGFRA 16.3%, wild-type 11.4%). The percentage of high risk patients in the different risk classifications varied from 19.9% to 38.0% depending on the used classification. Only 35.9% of patients had diagnosis or revision of pathology diagnosis within three months in a designated GIST referral centre. No increase in proportion of central pathology reviews was found. Proportion of patients with mutational analysis increased over the years. The registered incidence of GIST, 17.7 per million inhabitants in 2012 in the Netherlands, is still rising. Despite incorporation in the ESMO GIST guidelines since 2008 for mutational testing and since 2010 for central review of pathology, both are performed in a minority of patients.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Gastrointestinal Stromal Tumors/epidemiology ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/metabolism ; Gastrointestinal Stromal Tumors/pathology ; Humans ; Immunohistochemistry ; Incidence ; Male ; Middle Aged ; Mutation ; Netherlands/epidemiology ; Referral and Consultation/statistics & numerical data ; Registries ; Risk Assessment ; Young Adult
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2018-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-017-2285-x
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Article: Zebrafish as a model for human osteosarcoma.

Mohseny, A B / Hogendoorn, P C W

Advances in experimental medicine and biology

2014 Volume 804, Page(s) 221–236

Abstract: For various reasons involving biological comparativeness, expansive technological possibilities, accelerated experimental speed, and competitive costs, zebrafish has become a comprehensive model for cancer research. Hence, zebrafish embryos and full- ... ...

Abstract	For various reasons involving biological comparativeness, expansive technological possibilities, accelerated experimental speed, and competitive costs, zebrafish has become a comprehensive model for cancer research. Hence, zebrafish embryos and full-grown fish have been instrumental for studies of leukemia, melanoma, pancreatic cancer, bone tumors, and other malignancies. Although because of its similarities to human osteogenesis zebrafish appears to be an appealing model to investigate osteosarcoma, only a few osteosarcoma specific studies have been accomplished yet. Here, we review interesting related and unrelated reports of which the findings might be extrapolated to osteosarcoma. More importantly, rational but yet unexplored applications of zebrafish are debated to expand the window of opportunities for future establishment of osteosarcoma models. Accordingly technological advances of zebrafish based cancer research, such as robotic high-throughput multicolor injection systems and advanced imaging methods are discussed. Furthermore, various use of zebrafish embryos for screening drug regimens by combinations of chemotherapy, novel drug deliverers, and immune system modulators are suggested. Concerning the etiology, the high degree of genetic similarity between zebrafish and human cancers indicates that affected regions are evolutionarily conserved. Therefore, zebrafish as a swift model system that allows for the investigation of multiple candidate gene-defects is presented.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Bone Neoplasms/drug therapy ; Bone Neoplasms/genetics ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Disease Models, Animal ; Drug Delivery Systems ; Embryo, Nonmammalian ; Gene Expression Regulation, Neoplastic ; Humans ; Immunologic Factors/pharmacology ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Osteogenesis/drug effects ; Osteogenesis/genetics ; Osteosarcoma/drug therapy ; Osteosarcoma/genetics ; Osteosarcoma/metabolism ; Osteosarcoma/pathology ; Robotics ; Signal Transduction ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
Chemical Substances	Antineoplastic Agents ; Immunologic Factors ; Neoplasm Proteins ; Zebrafish Proteins
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-04843-7_12
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Article ; Online: Nikolay Ivanovich Pirogov (1810-1881): Anatomical research to develop surgery.

Hendriks, I F / Zhuravlev, D A / Bovill, J G / Boer, F / Gaivoronskii, I V / Hogendoorn, P C W / DeRuiter, M C

Clinical anatomy (New York, N.Y.)

2019 Volume 33, Issue 5, Page(s) 714–730

Abstract: The 19th century Russian surgeon Nikolay Ivanovich Pirogov believed passionately in the importance of anatomy for surgeons. His interest in anatomy began as a medical student in Moscow. After graduating in 1828 Pirogov entered the postgraduate German- ... ...

Abstract	The 19th century Russian surgeon Nikolay Ivanovich Pirogov believed passionately in the importance of anatomy for surgeons. His interest in anatomy began as a medical student in Moscow. After graduating in 1828 Pirogov entered the postgraduate German-Baltic University of Dorpat (now Tartu in the Republic of Estonia) where he studied anatomy and surgery. After completing his study, he remained to research the consequences of ligation of the aorta in a series of animal experiments, which formed the core of his doctoral thesis. He wanted to determine the feasibility of aortic ligation as a treatment for patients with an aneurysm of the aorta or iliac artery. He discovered that success was only likely when the aorta was ligated between the two mesenteric arteries and the ligature gradually tightened, an approach surgically difficult in humans. Pirogov then spent 2 years at the Charité Hospital in Berlin before returning to Russia. In 1841, he was appointed Professor of Applied Anatomy and Surgery at the Imperial Medico-Surgical Academy in Saint Petersburg. He instituted the teaching of microscopy and histology to the medical curriculum and in 1846 formed the Institute for Applied Anatomy within the academy, where in addition to teaching medical students future teachers of anatomy in Russia were trained. Pirogov published extensively on anatomy, including several anatomical atlases, the most notable his three-dimensional atlas of topographical anatomy published in four volumes between 1852 and 1859. Today Pirogov's contributions to anatomy are remembered in a number of anatomical structures named after him. Clin. Anat., 33:714-730, 2020. © 2019 Wiley Periodicals, Inc.
MeSH term(s)	Anatomy/history ; General Surgery/history ; History, 19th Century ; Humans ; Orthopedic Procedures/history
Language	English
Publishing date	2019-11-11
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article
ZDB-ID	1025505-9
ISSN	1098-2353 ; 0897-3806
ISSN (online)	1098-2353
ISSN	0897-3806
DOI	10.1002/ca.23493
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Zs.A 2592: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article: Conjunctival Leiomyosarcoma, a Rare Neoplasm Always Originating at the Limbus? Report of a New Case and Review of 11 Published Cases

De Groot, V. / Verhelst, E. / Hogendoorn, P.C.W. / de Keizer, R.J.W.

Ocular Oncology and Pathology

2019 Volume 5, Issue 5, Page(s) 333–339

Abstract: Purpose of the Study: To describe the differential diagnosis and management of a rare conjunctival malignancy. Procedures: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with ... ...

Institution	Department of Ophthalmology, University Hospital Antwerp, Antwerp, Belgium Antwerp University, Faculty of Medicine, Antwerp, Belgium ZNA Middelheim Hospital, Antwerp, Belgium
Abstract	Purpose of the Study: To describe the differential diagnosis and management of a rare conjunctival malignancy. Procedures: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with myogenic differentiation. Six months later, three suspect lesions developed at the border of the previous excision. Pathological diagnosis pointed to a leiomyosarcoma. Adjuvant radiotherapy with strontium-90 brachytherapy was applied. After 3 years, there was neither recurrence nor distant metastases. A literature review revealed 11 cases of conjunctival leiomyosarcoma. Results: All 12 cases seemed to originate at the limbal conjunctiva. Scleral invasion was found only in one patient with multiple previous resections. Corneal invasion was reported in two patients. Four patients had a globe-sparing resection. In two of them, margins were not tumor free and additional brachytherapy gave a tumor-free follow-up of 1 and 3 years. Four cases underwent an exenteration. Conclusion and Message: Primary conjunctival leiomyosarcoma is a rare tumor with a favorable prognosis due to early detection and consequently limited size. Diagnosis involves histopathological investigation including immunohistochemistry. If possible, complete resection has the best prognosis. Adjunctive radiotherapy can be effective when the margins are not free and should be considered.
Keywords	Leiomyosarcoma ; Conjunctival tumor ; Limbus ; Eye ; Orbit ; Soft tissue tumor
Language	English
Publishing date	2019-01-24
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Research Article
ZDB-ID	2806965-1
ISSN	2296-4657 ; 2296-4681
ISSN (online)	2296-4657
ISSN	2296-4681
DOI	10.1159/000494497
Database	Karger publisher's database

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Article ; Online: The adapter protein Myd88 plays an important role in limiting mycobacterial growth in a zebrafish model for tuberculosis.

Hosseini, Rohola / Lamers, Gerda E M / Bos, Erik / Hogendoorn, Pancras C W / Koster, Abraham J / Meijer, Annemarie H / Spaink, Herman P / Schaaf, Marcel J M

Virchows Archiv : an international journal of pathology

2021 Volume 479, Issue 2, Page(s) 265–275

Abstract: Tuberculosis (TB) is the most prevalent bacterial infectious disease in the world, caused by the pathogen Mycobacterium tuberculosis (Mtb). In this study, we have used Mycobacterium marinum (Mm) infection in zebrafish larvae as an animal model for this ... ...

Abstract	Tuberculosis (TB) is the most prevalent bacterial infectious disease in the world, caused by the pathogen Mycobacterium tuberculosis (Mtb). In this study, we have used Mycobacterium marinum (Mm) infection in zebrafish larvae as an animal model for this disease to study the role of the myeloid differentiation factor 88 (Myd88), the key adapter protein of Toll-like receptors. Previously, Myd88 has been shown to enhance innate immune responses against bacterial infections, and in the present study, we have investigated the effect of Myd88 deficiency on the granuloma morphology and the intracellular distribution of bacteria during Mm infection. Our results show that granulomas formed in the tail fin from myd88 mutant larvae have a more compact structure and contain a reduced number of leukocytes compared to the granulomas observed in wild-type larvae. These morphological differences were associated with an increased bacterial burden in the myd88 mutant. Electron microscopy analysis showed that the majority of Mm in the myd88 mutant are located extracellularly, whereas in the wild type, most bacteria were intracellular. In the myd88 mutant, intracellular bacteria were mainly present in compartments that were not electron-dense, suggesting that these compartments had not undergone fusion with a lysosome. In contrast, approximately half of the intracellular bacteria in wild-type larvae were found in electron-dense compartments. These observations in a zebrafish model for tuberculosis suggest a role for Myd88-dependent signalling in two important phenomena that limit mycobacterial growth in the infected tissue. It reduces the number of leukocytes at the site of infection and the acidification of bacteria-containing compartments inside these cells.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Bacterial Load ; Disease Models, Animal ; Granuloma/genetics ; Granuloma/metabolism ; Granuloma/microbiology ; Granuloma/pathology ; Hydrogen-Ion Concentration ; Leukocytes/metabolism ; Leukocytes/microbiology ; Leukocytes/ultrastructure ; Lysosomes/metabolism ; Lysosomes/microbiology ; Lysosomes/ultrastructure ; Microscopy, Electron, Transmission ; Mycobacterium Infections, Nontuberculous/genetics ; Mycobacterium Infections, Nontuberculous/metabolism ; Mycobacterium Infections, Nontuberculous/microbiology ; Mycobacterium Infections, Nontuberculous/pathology ; Mycobacterium marinum/growth & development ; Mycobacterium marinum/ultrastructure ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; Signal Transduction ; Tuberculosis/genetics ; Tuberculosis/metabolism ; Tuberculosis/microbiology ; Tuberculosis/pathology ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish/microbiology ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
Chemical Substances	MyD88 protein, zebrafish ; Myeloid Differentiation Factor 88 ; Zebrafish Proteins
Language	English
Publishing date	2021-02-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-021-03043-3
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