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After internalization, <jats:italic>Salmonella<\/jats:italic> sp. Manipulates several host processes, mainly through the activation of the type III secretion system (T3SS), including modification of host lipid metabolism and lipid droplet (LD) accumulation. LDs are dynamic and complex lipid\u2010rich organelles involved in several cellular processes. The present study investigated the mechanism involved in LD biogenesis in <jats:italic>Salmonella<\/jats:italic>\u2010infected macrophages and its role in bacterial pathogenicity. Here, we reported that <jats:italic>S<\/jats:italic>. Typhimurium induced a rapid time\u2010dependent increase of LD formation in macrophages. The LD biogenesis was demonstrated to depend on <jats:italic>Salmonella's<\/jats:italic> viability and SPI1\u2010related T3SS activity, with the participation of Toll\u2010Like Receptor (TLR) signaling. We also observed that LD accumulation occurs through TLR2\u2010dependent signaling and is counter\u2010regulated by TLR4. Last, the pharmacologic modulation of LD formation by inhibiting diacylglycerol <jats:italic>O<\/jats:italic>\u2010acyltransferase 1 (DGAT1) and cytosolic phospholipase A2 (cPLA2) significantly reduced the intracellular bacterial proliferation and impaired the prostaglandin E2 (PGE<jats:sub>2<\/jats:sub>) synthesis. Collectively, our data suggest the role of LDs on <jats:italic>S<\/jats:italic>. <jats:italic>typhimurium<\/jats:italic> intracellular survival and replication in macrophages. This data set provides new perspectives for future investigations about LDs in host\u2013pathogen interaction.<\/jats:p>","DOI":"10.1111\/mmi.14844","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T11:55:42Z","timestamp":1637063742000},"page":"293-306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Lipid droplet accumulation occurs early following <i>Salmonella<\/i> infection and contributes to intracellular bacterial survival and replication"],"prefix":"10.1111","volume":"117","author":[{"given":"Ellen","family":"Kiarely Souza","sequence":"first","affiliation":[{"name":"Laboratory of Immunopharmacology Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Program of Immunology and Inflammation Federal University of Rio de Janeiro UFRJ  Rio de Janeiro 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