The role of Lipid Droplets in the innate antibacterial activity of bone marrow murine macrophages

Recent studies indicate that the reprogramming of lipid metabolism is a central factor during inflammatory processes. Lipid droplets (LDs) are lipid-enriched dynamic organelles that store and provide lipid substrates for diverse molecular functions. Furthermore, these organelles have a central role as platforms involved in the pathogen-host relationship. Although several studies associated usurpation of LDs by pathogenic intracellular bacterias, our data suggests that the role of LDs in bacterial infections has a pro-host molecular potential, actively participating in the antibacterial innate response. The literature related to the LDs/extracellular bacteria relationship presents several crucial gaps to understand the pro-inflammatory and protective innate role of these organelles. The objective of this work was to evaluate the role of LD´s in the immunometabolic reprogramming and antimicrobial activity of murine macrophages. E. coli infection was carried out in vitro in macrophages derived from mouse bone marrow (CEUA-IOC-Fiocruz L005/20). The results show that the change in lipid metabolism induced by E. coli infection is associated with the pro-inflammatory profile of macrophages, a change that occurs towards the accumulation of LDs in these cells. This phenomenon was observed both in E. coli infected or LPS+INFy. Furthermore, our data reveal that modulation of LDs biogenesis affects the killing capacity of murine macrophages against E. coli infection. Moreover, inhibition of LDs accumulation impacts the proinflammatory and antibacterial response by inhibiting the synthesis of prostaglandin E₂ (PGE₂) and nitric oxide (NO) and decreasing the expression of antimicrobial proteins viperin and IRGM-3. Taken together, our data demonstrated that LDs play an important role in the innate antibacterial response of macrophages through their lipid mediator production machinery, as well as through the compartmentalization of antimicrobial proteins.