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Article ; Online: Targeting IL-1β in patients with advanced

Filaly, Hajar El / Outlioua, Ahmed / Medyouf, Hind / Guessous, Fadila / Akarid, Khadija

2022 Volume 17, Page(s) 633–641

Abstract: Helicobacter ... ...

Abstract	Helicobacter pylori
MeSH term(s)	Cytokines ; Gastric Mucosa ; Helicobacter Infections/complications ; Helicobacter Infections/drug therapy ; Helicobacter pylori ; Humans ; Interleukin-1beta ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/microbiology
Chemical Substances	Cytokines ; IL1B protein, human ; Interleukin-1beta
Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2254620-0
ISSN	1746-0921 ; 1746-0913
ISSN (online)	1746-0921
ISSN	1746-0913
DOI	10.2217/fmb-2021-0242
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Article ; Online: Type I and III interferons are good markers to monitor COVID-19 pathophysiology.

Darif, Dounia / Ejghal, Rajaâ / Desterke, Christophe / Outlioua, Ahmed / Hammi, Ikram / Lemrani, Meryem / Hilali, Farida / Guessous, Fadila / Zaid, Younes / Akarid, Khadija

Cytokine

2023 Volume 165, Page(s) 156172

Abstract: The COVID-19 pandemic has caused millions of deaths and has resulted in disastrous societal and economic impacts worldwide. During SARS-CoV-2 infection, abnormal levels of pro-inflammatory cytokines have been observed and were associated to the severity ... ...

Abstract	The COVID-19 pandemic has caused millions of deaths and has resulted in disastrous societal and economic impacts worldwide. During SARS-CoV-2 infection, abnormal levels of pro-inflammatory cytokines have been observed and were associated to the severity of the disease. Type I (-α/β) and Type III (IFN-λ) interferons are family members of cytokines that play an important role in fighting viral replication during the early phases of infection. The location and timing of the IFNs production have been shown to be decisive for the COVID-19 outcome. Despite the effectiveness of COVID-19 vaccines and with the emergence of new SARS-CoV-2 variants, a better understanding of the involvement of IFNs as players in antiviral immunity in the COVID-19 pathophysiology is necessary to implement additional potent prophylactic and/or therapeutic approaches. In this study, we investigated the role of type I and III IFN in COVID-19 pathophysiology. We first analyzed the IFN-α, IFN-β and IFN- λ mRNA expression in nasopharyngeal swabs and blood samples from Moroccan patients infected with SARS-CoV-2 and secondly correlated these IFNs expressions with COVID-19 clinical and biological parameters. Our results showed that in the upper airways of patients with mild, non-severe, or severe COVID-19 manifestations, the IFN- α, - β and - λ are expressed in the same manner as in controls. However, in blood samples their expression was downregulated in all groups. Univariate linear models with interferons as predictors to evaluate clinical-biological parameters highlighted that the main clinical-biological relations were found when testing: FiO2, Lymphocyte values and virus load. Furthermore, the multivariate models confirmed that quantifications of interferons during COVID-19 are good biological markers for tracking COVID-19 pathophysiology.
MeSH term(s)	Humans ; Interferons ; COVID-19 ; COVID-19 Vaccines ; Pandemics ; SARS-CoV-2 ; Antiviral Agents ; Cytokines ; Interferon-alpha ; Interferon Lambda ; Interferon Type I
Chemical Substances	Interferons (9008-11-1) ; COVID-19 Vaccines ; Antiviral Agents ; Cytokines ; Interferon-alpha ; Interferon Lambda ; Interferon Type I
Language	English
Publishing date	2023-03-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2023.156172
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Article ; Online: Leptospira interrogans Prevents Macrophage Cell Death and Pyroptotic IL-1β Release through Its Atypical Lipopolysaccharide.

Bonhomme, Delphine / Hernandez-Trejo, Veronica / Papadopoulos, Stylianos / Pigache, Rémi / Fanton d'Andon, Martine / Outlioua, Ahmed / Boneca, Ivo G / Werts, Catherine

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 210, Issue 4, Page(s) 459–474

Abstract: Leptospira interrogans are bacteria that can infect all vertebrates and are responsible for leptospirosis, a neglected zoonosis. Some hosts, such as humans, are susceptible to the disease, whereas mice are resistant and get chronically colonized. ... ...

Abstract	Leptospira interrogans are bacteria that can infect all vertebrates and are responsible for leptospirosis, a neglected zoonosis. Some hosts, such as humans, are susceptible to the disease, whereas mice are resistant and get chronically colonized. Although leptospires escape recognition by some immune receptors, they activate the NOD-like receptor pyrin 3-inflammasome and trigger IL-1β secretion. Classically, IL-1β secretion is associated with lytic inflammatory cell death called pyroptosis, resulting from cytosolic LPS binding to inflammatory caspases, such as caspase 11. Interestingly, we showed that L. interrogans and Leptospira biflexa do not trigger cell death in either murine, human, hamster, or bovine macrophages, escaping both pyroptosis and apoptosis. We showed, in murine cells, that the mild IL-1β secretion induced by leptospires occurred through nonlytic caspase 8-dependent gasdermin D pore formation and not through activation of caspase 11/noncanonical inflammasome. Strikingly, we demonstrated a potent antagonistic effect of pathogenic L. interrogans and their atypical LPS on spontaneous and Escherichia coli LPS-induced cell death. Indeed, LPS of L. interrogans efficiently prevents caspase 11 dimerization and subsequent massive gasdermin D cleavage. Finally, we showed that pyroptosis escape by leptospires prevents massive IL-1β release, and we consistently found no major role of IL-1R in controlling experimental leptospirosis in vivo. Overall, to our knowledge, our findings described a novel mechanism by which leptospires dampen inflammation, thus potentially contributing to their stealthiness.
MeSH term(s)	Animals ; Cattle ; Cricetinae ; Humans ; Mice ; Caspases/metabolism ; Gasdermins ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Leptospira interrogans/metabolism ; Leptospirosis/metabolism ; Leptospirosis/microbiology ; Lipopolysaccharides ; Macrophages ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Pyroptosis ; Cell Death
Chemical Substances	Caspases (EC 3.4.22.-) ; Gasdermins ; Inflammasomes ; Interleukin-1beta ; Lipopolysaccharides ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2023-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200584
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Article: IL-1 Polymorphism and

El Filaly, Hajar / Outlioua, Ahmed / Desterke, Christophe / Echarki, Zerif / Badre, Wafaa / Rabhi, Moncef / Riyad, Myriam / Arnoult, Damien / Khalil, Abdelouahed / Akarid, Khadija

Microorganisms

2023 Volume 11, Issue 2

Abstract: Genetic polymorphisms at the IL-1 cluster are associated with ... ...

Abstract	Genetic polymorphisms at the IL-1 cluster are associated with increased
Language	English
Publishing date	2023-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11020353
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Article: The Role of Optineurin in Antiviral Type I Interferon Production.

Outlioua, Ahmed / Pourcelot, Marie / Arnoult, Damien

Frontiers in immunology

2018 Volume 9, Page(s) 853

Abstract: After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I ... ...

Abstract	After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity. This review summarizes the sensing of viruses and the signaling leading to type I IFN production following TBK1 activation through its ubiquitination and the sensing of ubiquitin chains by OPTN at the Golgi apparatus.
MeSH term(s)	Animals ; Cell Cycle Proteins ; Golgi Apparatus/immunology ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-3/immunology ; Interferon Regulatory Factor-3/metabolism ; Interferon Regulatory Factor-7/immunology ; Interferon Regulatory Factor-7/metabolism ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Membrane Transport Proteins ; Mice ; Phosphorylation ; Protein Serine-Threonine Kinases/immunology ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; Transcription Factor TFIIIA/genetics ; Transcription Factor TFIIIA/immunology ; Ubiquitination ; Virus Diseases/immunology
Chemical Substances	Cell Cycle Proteins ; IRF7 protein, human ; Interferon Regulatory Factor-3 ; Interferon Regulatory Factor-7 ; Interferon Type I ; Membrane Transport Proteins ; OPTN protein, human ; Transcription Factor TFIIIA ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TBK1 protein, human (EC 2.7.11.1)
Language	English
Publishing date	2018-04-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00853
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Article ; Online: CXCL-8 as a signature of severe Helicobacter pylori infection and a stimulator of stomach region-dependent immune response.

El Filaly, Hajar / Desterke, Christophe / Outlioua, Ahmed / Badre, Wafaa / Rabhi, Moncef / Karkouri, Mehdi / Riyad, Myriam / Khalil, Abdelouahed / Arnoult, Damien / Akarid, Khadija

Clinical immunology (Orlando, Fla.)

2023 Volume 252, Page(s) 109648

Abstract: Helicobacter pylori infection is involved in development of diverse gastro-pathologies. Our aim is to investigate potential signature of cytokines-chemokine levels (IL-17A, IL-1β, and CXCL-8) in H. pylori-infected patients and their impact on immune ... ...

Abstract	Helicobacter pylori infection is involved in development of diverse gastro-pathologies. Our aim is to investigate potential signature of cytokines-chemokine levels (IL-17A, IL-1β, and CXCL-8) in H. pylori-infected patients and their impact on immune response in both corpus and antrum. Multivariate level analysis with machine learning model were carried out using cytokines/chemokine levels of infected Moroccan patients. In addition, Geo dataset was used to run enrichment analysis following CXCL-8 upregulation. Our analysis showed that combination of cytokines-chemokine levels allowed prediction of positive H. pylori density score with <5% of miss-classification error, with fundus CXCL-8 being the most important variable for this discrimination. Furthermore, CXCL-8 dependent expression profile was mainly associated to IL6/JAK/STAT3 signaling in the antrum, interferons alpha and gamma responses in the corpus and commonly induced transcriptional /proliferative activities. To conclude, CXCL-8 level might be a signature of Moroccan H. pylori-infected patients and an inducer of regional-dependent immune response at the gastric level. Larger trials must be carried out to validate the relevance of these results for diverse populations.
MeSH term(s)	Humans ; Cytokines/metabolism ; Gastric Mucosa/metabolism ; Gastric Mucosa/pathology ; Helicobacter Infections/metabolism ; Helicobacter Infections/pathology ; Helicobacter pylori/metabolism ; Immunity ; Stomach/pathology
Chemical Substances	Cytokines ; CXCL8 protein, human
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109648
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Article ; Online: RNA viruses promote activation of the NLRP3 inflammasome through cytopathogenic effect-induced potassium efflux.

da Costa, Leandro Silva / Outlioua, Ahmed / Anginot, Adrienne / Akarid, Khadija / Arnoult, Damien

Cell death & disease

2019 Volume 10, Issue 5, Page(s) 346

Abstract: Early detection of viruses by the innate immune system is crucial for host defense. The NLRP3 inflammasome, through activation of caspase-1, promotes the maturation of IL-1β and IL-18, which are critical for antiviral immunity and inflammatory response. ... ...

Abstract	Early detection of viruses by the innate immune system is crucial for host defense. The NLRP3 inflammasome, through activation of caspase-1, promotes the maturation of IL-1β and IL-18, which are critical for antiviral immunity and inflammatory response. However, the mechanism by which viruses activate this inflammasome is still debated. Here, we report that the replication of cytopathogenic RNA viruses such as vesicular stomatitis virus (VSV) or encephalomyocarditis virus (EMCV) induced a lytic cell death leading to potassium efflux, the common trigger of NLRP3 inflammasome activation. This lytic cell death was not prevented by a chemical or genetic inhibition of apoptosis, pyroptosis, or necroptosis but required the viral replication. Hence, the viruses that stimulated type I IFNs production after their sensing did not activate NLRP3 inflammasome due to an inhibition of their replication. In contrast, NLRP3 inflammasome activation induced by RNA virus infection was stimulated in IFNAR-deficient or MAVS-deficient cells consequently to an increased viral replication and ensuing lytic cell death. Therefore, in a context of inefficient IFN response, viral replication-induced lytic cell death activates of the NLRP3 inflammasome to fight against infection.
MeSH term(s)	Adaptor Proteins, Signal Transducing/deficiency ; Adaptor Proteins, Signal Transducing/genetics ; Animals ; Bone Marrow Cells/cytology ; Dynamins/antagonists & inhibitors ; Dynamins/genetics ; Dynamins/metabolism ; Encephalomyocarditis virus/physiology ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/analysis ; Interleukin-1beta/metabolism ; Lipopolysaccharides/pharmacology ; Macrophages/cytology ; Macrophages/metabolism ; Macrophages/virology ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Necroptosis ; Potassium/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Receptor, Interferon alpha-beta/deficiency ; Receptor, Interferon alpha-beta/genetics ; Vesiculovirus/physiology ; Virus Replication
Chemical Substances	Adaptor Proteins, Signal Transducing ; IPS-1 protein, mouse ; Ifnar2 protein, mouse ; Inflammasomes ; Interleukin-1beta ; Lipopolysaccharides ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Small Interfering ; Receptor, Interferon alpha-beta (156986-95-7) ; Dnm1l protein, mouse (EC 3.6.5.5) ; Dynamins (EC 3.6.5.5) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2019-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-019-1579-0
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Article ; Online: Possible introduction of

Baghad, Bouchra / Razanapinaritra, Rojosoa / Maksouri, Hasnaa / El Bouri, Hicham / Outlioua, Ahmed / Fellah, Hassan / Lemrani, Meryem / Akarid, Khadija / Martin-Sanchez, Joaquina / Chiheb, Soumiya / Riyad, Myriam

Parasite epidemiology and control

2020 Volume 9, Page(s) e00129

Abstract: Leishmaniases are a group of infectious diseases caused by ... ...

Abstract	Leishmaniases are a group of infectious diseases caused by protozoan
Language	English
Publishing date	2020-01-03
Publishing country	Netherlands
Document type	Journal Article
ISSN	2405-6731
ISSN (online)	2405-6731
DOI	10.1016/j.parepi.2019.e00129
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Article: Possible introduction of Leishmania tropica to urban areas determined by epidemiological and clinical profiles of patients with cutaneous leishmaniasis in Casablanca (Morocco)

Parasite epidemiology and control. 2020 May, v. 9

2020

Abstract: Leishmaniases are a group of infectious diseases caused by protozoan Leishmania parasites and are transmitted by the bites of infected phlebotomine sandflies. The heterogeneity of these diseases is influenced by both parasitic properties and host factors. ...

Abstract	Leishmaniases are a group of infectious diseases caused by protozoan Leishmania parasites and are transmitted by the bites of infected phlebotomine sandflies. The heterogeneity of these diseases is influenced by both parasitic properties and host factors. Cutaneous leishmaniasis (CL) is a major public health problem in Morocco, where the geographical expansion of CL (particularly CL caused by Leishmania tropica), the heterogeneous appearance of lesions and the difficulty in diagnosing CL contribute to late diagnosis of CL and delayed treatment of patients. Therefore, the main objective of this study was to describe the epidemiological and clinical profiles of patients with CL diagnosed in Casablanca (Morocco), which is a non-endemic area for CL. A cross-sectional study was conducted between 2010 and 2016, during which epidemiological and clinical data were collected from patients that met the inclusion criteria through an information sheet. Then, samples were obtained from each patient for parasitological and molecular diagnosis, and only patients with positive polymerase chain reaction and genotyping results were included in the study. Overall, 106 cases of CL were genotyped, of which 61 (57.5%) were caused by L. tropica, 38 (35.9%) by L. major and 7 (6.6%) by L. infantum. While all age groups were affected, CL cases wherein L. tropica was the causative agent were most frequently diagnosed in children aged 0–9 years (p = 0.005), whereas those caused by L. major were more frequently diagnosed in elderly patients (p = 0.004). Multivariate logistic regression analysis showed that two clinical variables were significantly associated with CL caused by L. tropica: lesion size (p = 0.002) and occurrence of lesion on the face (p = 0.005). Furthermore, the results of our survey highlighted the association of Leishmania infection when travelling to endemic areas. The high number of endemic foci where patients with CL were infected with L. tropica illustrated the tendency of this form to spread and generate epidemics, exposing young people to a greater degree to the disease. The epidemic status of CL caused by L. tropica in Morocco and the increased movement of the population from rural to urban areas indicate a possible introduction of this species to urban areas.
Keywords	Leishmania tropica ; Phlebotominae ; cross-sectional studies ; cutaneous leishmaniasis ; elderly ; etiological agents ; face ; genotyping ; parasites ; patients ; people ; polymerase chain reaction ; public health ; regression analysis ; surveys ; Morocco
Language	English
Dates of publication	2020-05
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ISSN	2405-6731
DOI	10.1016/j.parepi.2019.e00129
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Gastric IL-1β, IL-8, and IL-17A expression in Moroccan patients infected with Helicobacter pylori may be a predictive signature of severe pathological stages.

Outlioua, Ahmed / Badre, Wafaa / Desterke, Christophe / Echarki, Zerif / El Hammani, Nadira / Rabhi, Monsef / Riyad, Myriam / Karkouri, Mehdi / Arnoult, Damien / Khalil, Abdelouahed / Akarid, Khadija

Cytokine

2019 Volume 126, Page(s) 154893

Abstract: Introduction: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, ...

Abstract	Introduction: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, leading to pro-inflammatory cytokines production and immune cells recruitment. Various studies have shown that there are ethnic- and population-related differences in the expression of these cytokines. Although the H. pylori infection is a major public health problem in Morocco, to our knowledge, no study has been carried out in gastric cytokine expression from H. pylori-infected Moroccan patients. Thus we aimed to (i) determine the IL-1β, IL-8 and IL-17A gene expression in gastric biopsies from Moroccan patients infected with H. pylori, and (ii) to determine the cytokine signature of each pathological stages associated with this infection. Material and methods: 71 patients with epigastralgic pain were included in this study. The H. pylori detection on gastric biopsies was performed by histopathological and PCR analysis. The IL-1β, IL-8 and IL-17A mRNA expression in the antrun and fundus biopsies was performed by RT-qPCR. Results: The histopathological and PCR analyses revealed that 87.32% of the patients were infected with H. pylori. IL-1β mRNA expression was significantly lower in the antral mucosa of H. pylori-infected patients (p = 0.0038) than in the uninfected while there was no significant difference in the expression of IL-8 and IL-17A mRNA. The expression of the three cytokines was higher in the fundic mucosa of H. pylori-infected patients than in the uninfected patients, but only IL-8 and IL-17A expression reached statistical significance (p = 0.042 and p = 0.0179 respectively). Furthermore, the multivariate predictive analysis highlighted a cytokine signature that may predict metaplasia during the infection progression that involves a specific down-regulation of IL17A and an up-regulation of IL1β in antral and fundic metaplasia respectively.
MeSH term(s)	Adult ; Female ; Gastric Mucosa/immunology ; Gastric Mucosa/microbiology ; Gastric Mucosa/pathology ; Gastritis/diagnosis ; Gastritis/microbiology ; Gastritis/pathology ; Helicobacter Infections/diagnosis ; Helicobacter Infections/pathology ; Helicobacter pylori/immunology ; Humans ; Interleukin-17/analysis ; Interleukin-1beta/analysis ; Interleukin-8/analysis ; Male ; Middle Aged ; Morocco ; Signal Transduction/immunology ; Stomach Neoplasms/microbiology ; Stomach Neoplasms/pathology
Chemical Substances	CXCL8 protein, human ; IL17A protein, human ; IL1B protein, human ; Interleukin-17 ; Interleukin-1beta ; Interleukin-8
Language	English
Publishing date	2019-12-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2019.154893
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