PMID- 36579614 OWN - NLM STAT- MEDLINE DCOM- 20230314 LR - 20230316 IS - 1365-2958 (Electronic) IS - 0950-382X (Linking) VI - 119 IP - 2 DP - 2023 Feb TI - Mycobacterium tuberculosis induces delayed lipid droplet accumulation in dendritic cells depending on bacterial viability and virulence. PG - 224-236 LID - 10.1111/mmi.15023 [doi] AB - 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. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Costa, Maria Fernanda de Souza AU - Costa MFS AUID- ORCID: 0000-0003-2300-5384 AD - Instituto de Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Niteroi, Brazil. AD - Center for Technological Development in Health, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. FAU - Pereira-Dutra, Filipe AU - Pereira-Dutra F AUID- ORCID: 0000-0003-1917-2876 AD - Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. FAU - Deboosere, Nathalie AU - Deboosere N AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. FAU - Jouny, Samuel AU - Jouny S AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. FAU - Song, Ok-Ryul AU - Song OR AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. FAU - Iack, Guilherme AU - Iack G AD - Instituto de Biologia, Departamento de Imunobiologia, Universidade Federal Fluminense, Niteroi, Brazil. AD - Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. FAU - Souza, Andreia Lamoglia AU - Souza AL AD - Fundacao Oswaldo Cruz, Laboratory of Immunology and Immunogenetics in Infectious Diseases at Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil. FAU - Roma, Eric Henrique AU - Roma EH AD - Fundacao Oswaldo Cruz, Laboratory of Immunology and Immunogenetics in Infectious Diseases at Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil. FAU - Delorme, Vincent AU - Delorme V AUID- ORCID: 0000-0001-5235-7069 AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. FAU - Bozza, Patricia T AU - Bozza PT AD - Immunopharmacology Laboratory, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. FAU - Brodin, Priscille AU - Brodin P AD - Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230116 PL - England TA - Mol Microbiol JT - Molecular microbiology JID - 8712028 RN - 0 (BCG Vaccine) SB - IM MH - *Mycobacterium tuberculosis/genetics MH - Lipid Droplets MH - Virulence MH - Microbial Viability MH - BCG Vaccine/metabolism MH - Dendritic Cells/metabolism/microbiology OTO - NOTNLM OT - RD1 OT - dendritic cell OT - immunometabolism OT - lipid droplets OT - tuberculosis EDAT- 2022/12/30 06:00 MHDA- 2023/03/15 06:00 CRDT- 2022/12/29 04:35 PHST- 2022/12/23 00:00 [revised] PHST- 2021/11/30 00:00 [received] PHST- 2022/12/25 00:00 [accepted] PHST- 2022/12/30 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2022/12/29 04:35 [entrez] AID - 10.1111/mmi.15023 [doi] PST - ppublish SO - Mol Microbiol. 2023 Feb;119(2):224-236. doi: 10.1111/mmi.15023. Epub 2023 Jan 16.