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Article ; Online: Host Immunity Influences the Composition of Murine Gut Microbiota.

Van Averbeke, Vincent / Berkell, Matilda / Mysara, Mohamed / Rodriguez-Ruiz, Juan Pablo / Xavier, Basil Britto / De Winter, Fien H R / Jongers, Bart 's / Jairam, Ravi Kumar / Hotterbeekx, An / Goossens, Herman / Cohen, E Suzanne / Malhotra-Kumar, Surbhi / Kumar-Singh, Samir

Frontiers in immunology

2022 Volume 13, Page(s) 828016

Abstract: The influence of gut microbiota on host immunity is widely studied, and its disturbance has been linked to several immune-mediated disorders. Conversely, whether and how inherently disturbed canonical Th1 (pro-inflammatory) and/or Th2 (anti-inflammatory) ...

Abstract	The influence of gut microbiota on host immunity is widely studied, and its disturbance has been linked to several immune-mediated disorders. Conversely, whether and how inherently disturbed canonical Th1 (pro-inflammatory) and/or Th2 (anti-inflammatory) immune pathways modify the host microbiome is not sufficiently investigated. Here, we characterized the humoral, cellular, and cytokine immunity, and associated alterations in gut microbiota of naïve wild-type mice (C57BL/6 and BALB/c), and mice with deficiencies in Th2 responses (IL-4Rα and IL-33 knockout mice) or in both Th1 and Th2 responses (NOD
MeSH term(s)	Animals ; Cytokines ; Gastrointestinal Microbiome ; Interleukin-33 ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics
Chemical Substances	Cytokines ; Interleukin-33 ; RNA, Ribosomal, 16S
Language	English
Publishing date	2022-03-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.828016
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Article ; Online: Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments

Akshita Gupta / Angelina Konnova / Mathias Smet / Matilda Berkell / Alessia Savoldi / Matteo Morra / Vincent Van averbeke / Fien H.R. De Winter / Denise Peserico / Elisa Danese / An Hotterbeekx / Elda Righi / mAb ORCHESTRA working group / Pasquale De Nardo / Evelina Tacconelli / Surbhi Malhotra-Kumar / Samir Kumar-Singh

The Journal of Clinical Investigation, Vol 133, Iss

2023 Volume 6

Abstract: ... sotrovimab were longitudinally studied over 28 days for viral loads, de novo Spike mutations, mAb kinetics ... of developing de novo Spike mutations. Development of escape mutants also strongly correlated with neutralizing ...

Abstract	Background The role of host immunity in emergence of evasive SARS-CoV-2 Spike mutations under therapeutic monoclonal antibody (mAb) pressure remains to be explored.Methods In a prospective, observational, monocentric ORCHESTRA cohort study, conducted between March 2021 and November 2022, mild-to-moderately ill COVID-19 patients (n = 204) receiving bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab were longitudinally studied over 28 days for viral loads, de novo Spike mutations, mAb kinetics, seroneutralization against infecting variants of concern, and T cell immunity. Additionally, a machine learning–based circulating immune-related biomarker (CIB) profile predictive of evasive Spike mutations was constructed and confirmed in an independent data set (n = 19) that included patients receiving sotrovimab or tixagevimab/cilgavimab.Results Patients treated with various mAbs developed evasive Spike mutations with remarkable speed and high specificity to the targeted mAb-binding sites. Immunocompromised patients receiving mAb therapy not only continued to display significantly higher viral loads, but also showed higher likelihood of developing de novo Spike mutations. Development of escape mutants also strongly correlated with neutralizing capacity of the therapeutic mAbs and T cell immunity, suggesting immune pressure as an important driver of escape mutations. Lastly, we showed that an antiinflammatory and healing-promoting host milieu facilitates Spike mutations, where 4 CIBs identified patients at high risk of developing escape mutations against therapeutic mAbs with high accuracy.Conclusions Our data demonstrate that host-driven immune and nonimmune responses are essential for development of mutant SARS-CoV-2. These data also support point-of-care decision making in reducing the risk of mAb treatment failure and improving mitigation strategies for possible dissemination of escape SARS-CoV-2 mutants.Funding The ORCHESTRA project/European Union’s Horizon 2020 research and innovation ...
Keywords	COVID-19 ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
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Article ; Online: Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient

Rachel M. Wheatley / Julio Diaz Caballero / Thomas E. van der Schalk / Fien H. R. De Winter / Liam P. Shaw / Natalia Kapel / Claudia Recanatini / Leen Timbermont / Jan Kluytmans / Mark Esser / Alicia Lacoma / Cristina Prat-Aymerich / Antonio Oliver / Samir Kumar-Singh / Surbhi Malhotra-Kumar / R. Craig MacLean

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs. ...

Abstract	In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs.
Keywords	Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient.

Wheatley, Rachel M / Caballero, Julio Diaz / van der Schalk, Thomas E / De Winter, Fien H R / Shaw, Liam P / Kapel, Natalia / Recanatini, Claudia / Timbermont, Leen / Kluytmans, Jan / Esser, Mark / Lacoma, Alicia / Prat-Aymerich, Cristina / Oliver, Antonio / Kumar-Singh, Samir / Malhotra-Kumar, Surbhi / Craig MacLean, R

Nature communications

2022 Volume 13, Issue 1, Page(s) 6523

Abstract: Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa ... ...

Abstract	Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients.
MeSH term(s)	Humans ; Pseudomonas aeruginosa/genetics ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Meropenem/pharmacology ; Lung ; Bacteria ; Intensive Care Units
Chemical Substances	Anti-Bacterial Agents ; Meropenem (FV9J3JU8B1)
Language	English
Publishing date	2022-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34101-2
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Article: Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis.

Claesen, Karen / Sim, Yani / Bracke, An / De Bruyn, Michelle / De Hert, Emilie / Vliegen, Gwendolyn / Hotterbeekx, An / Vujkovic, Alexandra / van Petersen, Lida / De Winter, Fien H R / Brosius, Isabel / Theunissen, Caroline / van Ierssel, Sabrina / van Frankenhuijsen, Maartje / Vlieghe, Erika / Vercauteren, Koen / Kumar-Singh, Samir / De Meester, Ingrid / Hendriks, Dirk

Journal of clinical medicine

2022 Volume 11, Issue 6

Abstract: Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11061494
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Article ; Online: Proline-specific peptidase activities (DPP4, PRCP, FAP and PREP) in plasma of hospitalized COVID-19 patients.

Bracke, An / De Hert, Emilie / De Bruyn, Michelle / Claesen, Karen / Vliegen, Gwendolyn / Vujkovic, Alexandra / van Petersen, Lida / De Winter, Fien H R / Hotterbeekx, An / Brosius, Isabel / Theunissen, Caroline / Van Ierssel, Sabrina / van Frankenhuijsen, Maartje / Vlieghe, Erika / Vercauteren, Koen / Van der Veken, Pieter / Hendriks, Dirk / Kumar-Singh, Samir / De Meester, Ingrid

Clinica chimica acta; international journal of clinical chemistry

2022 Volume 531, Page(s) 4–11

Abstract: Background: COVID-19 patients experience several features of dysregulated immune system observed in sepsis. We previously showed a dysregulation of several proline-selective peptidases such as dipeptidyl peptidase 4 (DPP4), fibroblast activation protein ...

Abstract	Background: COVID-19 patients experience several features of dysregulated immune system observed in sepsis. We previously showed a dysregulation of several proline-selective peptidases such as dipeptidyl peptidase 4 (DPP4), fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP) and prolylcarboxypeptidase (PRCP) in sepsis. In this study, we investigated whether these peptidases are similarly dysregulated in hospitalized COVID-19 patients. Methods: Fifty-six hospitalized COVID-19 patients and 32 healthy controls were included. Enzymatic activities of DPP4, FAP, PREP and PRCP were measured in samples collected shortly after hospital admission and in longitudinal follow-up samples. Results: Compared to healthy controls, both DPP4 and FAP activities were significantly lower in COVID-19 patients at hospital admission and FAP activity further decreased significantly in the first week of hospitalization. While PRCP activity remained unchanged, PREP activity was significantly increased in COVID-19 patients at hospitalization and further increased during hospital stay and stayed elevated until the day of discharge. Conclusion: The changes in activities of proline-selective peptidases in plasma are very similar in COVID-19 and septic shock patients. The pronounced decrease in FAP activity deserves further investigation, both from a pathophysiological viewpoint and as its utility as a part of a biomarker panel.
MeSH term(s)	COVID-19 ; Carboxypeptidases ; Dipeptidyl Peptidase 4 ; Endopeptidases ; Gelatinases ; Humans ; Membrane Proteins ; Peptide Hydrolases ; Proline ; Serine Endopeptidases ; Shock, Septic
Chemical Substances	Membrane Proteins ; Proline (9DLQ4CIU6V) ; Carboxypeptidases (EC 3.4.-) ; Endopeptidases (EC 3.4.-) ; Peptide Hydrolases (EC 3.4.-) ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; lysosomal Pro-X carboxypeptidase (EC 3.4.16.2) ; Serine Endopeptidases (EC 3.4.21.-) ; fibroblast activation protein alpha (EC 3.4.21.-) ; Gelatinases (EC 3.4.24.-)
Language	English
Publishing date	2022-03-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2022.03.005
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Article ; Online: Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis

Karen Claesen / Yani Sim / An Bracke / Michelle De bruyn / Emilie De Hert / Gwendolyn Vliegen / An Hotterbeekx / Alexandra Vujkovic / Lida van Petersen / Fien H. R. De Winter / Isabel Brosius / Caroline Theunissen / Sabrina van Ierssel / Maartje van Frankenhuijsen / Erika Vlieghe / Koen Vercauteren / Samir Kumar-Singh / Ingrid De Meester / Dirk Hendriks

Journal of Clinical Medicine, Vol 11, Iss 1494, p

2022 Volume 1494

Abstract	Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.
Keywords	carboxypeptidase B2 ; carboxypeptidase U ; coronavirus ; COVID-19 ; thrombin-activatable fibrinolysis inhibitor ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Immunoglobin G/total antibody testing for SARS-CoV-2: A prospective cohort study of ambulatory patients and health care workers in two Belgian oncology units comparing three commercial tests.

van Dam, Peter / Huizing, Manon / Roelant, Ella / Hotterbeekx, An / De Winter, Fien H R / Kumar-Singh, Samir / Moons, Pieter / Amajoud, Zainab / Vulsteke, Christof / Croes, Lieselot / Janssens, Annelies / Berneman, Zwi / Prenen, Hans / Meuris, Leander / Vanden Berghe, Wim / Smits, Evelien / Peeters, Marc

European journal of cancer (Oxford, England : 1990)

2021 Volume 148, Page(s) 328–339

Abstract: ... by Elecsys® (R; Roche).: Results: In the overall study population IgG/total SARS-CoV-2 antibodies were ... R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT ... PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ ...

Abstract	Background: Coronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic. Methods: 922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity® (A; Abbott) and Liaison® (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys® (R; Roche). Results: In the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher's exact test p = 0.00001, p = 0.046, p = 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher's exact test p = 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test = 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test = <0.0001 for both). The rate of seroconversion (>75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test = 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N = 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001). Conclusion: HCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.
MeSH term(s)	Adolescent ; Aged ; Ambulatory Care ; Antibodies, Viral/immunology ; Belgium/epidemiology ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Case-Control Studies ; Child ; Child, Preschool ; Cohort Studies ; Female ; Health Personnel/statistics & numerical data ; Humans ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Neoplasms/epidemiology ; Neoplasms/immunology ; Oncology Service, Hospital ; Prospective Studies ; Reagent Kits, Diagnostic ; Reproducibility of Results ; SARS-CoV-2 ; Seroconversion ; Seroepidemiologic Studies
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Reagent Kits, Diagnostic
Language	English
Publishing date	2021-02-27
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2021.02.024
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Article: Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients.

Cancers

2021 Volume 13, Issue 22

Abstract: Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in ... ...

Abstract	Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (
Language	English
Publishing date	2021-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13225718
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Article ; Online: Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia.

De Winter, Fien H. R. / 's Jongers, Bart / Bielen, Kenny / Mancuso, Domenico / Timbermont, Leen / Lammens, Christine / Van Averbeke, Vincent / Boddaert, Jan / Ali, Omar / Kluytmans, Jan / Ruzin, Alexey / Malhotra-Kumar, Surbhi / Jorens, Philippe G / Goossens, Herman / Kumar-Singh, Samir

International journal of molecular sciences

2019 Volume 20, Issue 20

Abstract: Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked ...

Abstract	Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacterial phagocytic capacity of rodent lung macrophages. Since IL-4 is known to downregulate both Th1 and Th17 cytokines, the latter is important in mediating mucosal immunity and combating bacterial and fungal growth, we studied and showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22) were significantly upregulated in the lung as a response to different MV strategies currently utilized in clinic. To study whether the increased IL-4 levels are associated with downregulation of the anti-bacterial Th17 cytokines, we subsequently challenged mechanically ventilated rats with an intratracheal inoculation of
MeSH term(s)	Aged ; Animals ; Female ; Humans ; Interleukin-17/genetics ; Interleukin-17/metabolism ; Male ; Middle Aged ; Pneumonia, Ventilator-Associated/metabolism ; Rats ; Rats, Wistar ; Th17 Cells/metabolism ; Up-Regulation
Chemical Substances	Interleukin-17
Language	English
Publishing date	2019-10-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20205072
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