|
|||||
|
|
Mycobacterium tuberculosis induces delayed lipid droplet accumulation in dendritic cells depending on bacterial viability and virulence |
|
| Authors: | Maria Fernanda de Souza Costa Filipe Pereira-Dutra Nathalie Deboosere Samuel Jouny Ok-Ryul Song Guilherme Iack Andreia Lamoglia Souza Eric Henrique Roma Vincent Delorme Patricia T. Bozza Priscille Brodin |
| Affiliation: | 1. Instituto de Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Niteroi, Brazil;2. Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;3. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France Contribution: Formal analysis, Investigation, Methodology, Writing - review & editing;4. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France Contribution: Methodology;5. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France Contribution: Formal analysis, Methodology, Writing - review & editing;6. Instituto de Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Niteroi, Brazil Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil Contribution: Methodology;7. Fundação Oswaldo Cruz, Laboratory of Immunology and Immunogenetics in Infectious Diseases at Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil Contribution: Methodology;8. Fundação Oswaldo Cruz, Laboratory of Immunology and Immunogenetics in Infectious Diseases at Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil Contribution: Methodology, Resources;9. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France;10. Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil Contribution: Resources, Writing - review & editing;11. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France Contribution: Conceptualization, Funding acquisition, Resources, Supervision, Writing - review & editing |
| Abstract: | Tuberculosis remains a global health threat with high morbidity. Dendritic cells (DCs) participate in the acute and chronic inflammatory responses to Mycobacterium tuberculosis (Mtb) by directing the adaptive immune response and are present in lung granulomas. In macrophages, the interaction of lipid droplets (LDs) with mycobacteria-containing phagosomes is central to host-pathogen interactions. However, the data available for DCs are still a matter of debate. Here, we reported that bone marrow-derived DCs (BMDCs) were susceptible to Mtb infection and replication at similar rate to macrophages. Unlike macrophages, the analysis of gene expression showed that Mtb infection induced a delayed increase in lipid droplet-related genes and proinflammatory response. Hence, LD accumulation has been observed by high-content imaging in late periods. Infection of BMDCs with killed H37Rv demonstrated that LD accumulation depends on Mtb viability. Moreover, infection with the attenuated strains H37Ra and Mycobacterium bovis-BCG induced only an early transient increase in LDs, whereas virulent Mtb also induced delayed LD accumulation. In addition, infection with the BCG strain with the reintroduced virulence RD1 locus induced higher LD accumulation and bacterial replication when compared to parental BCG. Collectively, our data suggest that delayed LD accumulation in DCs is dependent on mycobacterial viability and virulence. |
| Keywords: | dendritic cell immunometabolism lipid droplets RD1 tuberculosis |