Dataset Information

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.

ABSTRACT: The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14⁺ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10^-/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.

SUBMITTER: Genoula M

PROVIDER: S-EPMC5854656 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.

Genoula Melanie M Marín Franco José Luis JL Dupont Maeva M Kviatcovsky Denise D Milillo Ayelén A Schierloh Pablo P Moraña Eduardo Jose EJ Poggi Susana S Palmero Domingo D Mata-Espinosa Dulce D González-Domínguez Erika E León Contreras Juan Carlos JC Barrionuevo Paula P Rearte Bárbara B Córdoba Moreno Marlina Olyissa MO Fontanals Adriana A Crotta Asis Agostina A Gago Gabriela G Cougoule Céline C Neyrolles Olivier O Maridonneau-Parini Isabelle I Sánchez-Torres Carmen C Hernández-Pando Rogelio R Vérollet Christel C Lugo-Villarino Geanncarlo G Sasiain María Del Carmen MDC Balboa Luciana L

Frontiers in immunology 20180309

The ability of <i>Mycobacterium tuberculosis</i> (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fra ...[more]

PMID: 29593722

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Project description:Background and objectivePleural effusions (PEs) are commonly seen in various pathologies and have a significant impact on patient health and quality of life. Unlike for malignant PEs, non-malignant PEs (NMPEs) do not have well-established guidelines. Much of the evidence base in this field is from a handful of randomised controlled trials (RCTs) and the majority are from retrospective cohort analyses and cases series. Cardiac related PEs fall within the entity of NMPEs and the aim of this narrative review is to gather the existing evidence in the field of congestive heart failure (CHF), pericarditis and post-cardiac injury syndrome (PCIS). This narrative review investigates the pathophysiology, diagnostic criteria and treatment options for the various cause of cardiac related PEs.MethodsThis narrative review is based on a comprehensive literature search analysing RCTs, prospective and retrospective cohort analyses and published case series.Key content and findingsCHF related PEs have a substantial mortality rate and carry a worse prognosis if the PEs are bilateral and transudative in nature. Light's criteria have often shown to misclassify transudative effusions in CHF (pseudo-exudates) and hence measuring serum-pleural albumin gradient is an invaluable tool to accurately identify transudates. Elevated serum and pleural N-terminal pro-B type natriuretic peptide (NT-proBNP) has shown increasing evidence of correctly identifying PEs secondary to CHF. However, they should be considered with the pre-test probability of CHF. Therapeutic thoracentesis and indwelling pleural catheter (IPC) placement may be necessary if medical management has failed. PEs can also occur secondary to pericarditis and are often small, bilateral and exudative. PCIS also results in PEs and are commonly seen in post-coronary artery bypass graft (CABG) surgery. Both entities need management of the underlying cause first, but in cases where PEs are refractory, individualised pleural interventions may be necessary.ConclusionsThis comprehensive narrative review provides valuable insights into the aetiology, diagnosis and management of PEs secondary to CHF, pericarditis and PCIS. The aim is to enhance the clinicians' knowledge of this complex and controversial topic to improve patient care of cardiac-related PEs. Ongoing trials in this field will be able to provide valuable insights.

Dataset Information

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.

Publications

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.

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