10.3389/fimmu.2018.00459.s001
Melanie Genoula
Melanie
Genoula
José Luis Marín Franco
José Luis Marín
Franco
Maeva Dupont
Maeva
Dupont
Denise Kviatcovsky
Denise
Kviatcovsky
Ayelén Milillo
Ayelén
Milillo
Pablo Schierloh
Pablo
Schierloh
Eduardo Jose Moraña
Eduardo Jose
Moraña
Susana Poggi
Susana
Poggi
Domingo Palmero
Domingo
Palmero
Dulce Mata-Espinosa
Dulce
Mata-Espinosa
Erika González-Domínguez
Erika
González-Domínguez
Juan Carlos León Contreras
Juan Carlos León
Contreras
Paula Barrionuevo
Paula
Barrionuevo
Bárbara Rearte
Bárbara
Rearte
Marlina Olyissa Córdoba Moreno
Marlina Olyissa Córdoba
Moreno
Adriana Fontanals
Adriana
Fontanals
Agostina Crotta Asis
Agostina Crotta
Asis
Gabriela Gago
Gabriela
Gago
Céline Cougoule
Céline
Cougoule
Olivier Neyrolles
Olivier
Neyrolles
Isabelle Maridonneau-Parini
Isabelle
Maridonneau-Parini
Carmen Sánchez-Torres
Carmen
Sánchez-Torres
Rogelio Hernández-Pando
Rogelio
Hernández-Pando
Christel Vérollet
Christel
Vérollet
Geanncarlo Lugo-Villarino
Geanncarlo
Lugo-Villarino
María del Carmen Sasiain
María
del Carmen Sasiain
Luciana Balboa
Luciana
Balboa
image_1.tif
Frontiers
2018
ACAT
interleukin-10
foamy macrophages
lipids
signal transducer and activator of transcription 3
tuberculosis
2018-03-09 04:05:45
Figure
https://frontiersin.figshare.com/articles/figure/image_1_tif/5965588
<p>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<sup>+</sup> 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<sup>−/−</sup> 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.</p>