Characterize febrile temperature dependency of anti-infection pathways in Salmonella-infected mouse macrophages

The influence of fever on the initiation phase of anti-infection immune responses, which involve mainly macrophages, has not been well studied. RAW264.7 macrophages were inoculated with Salmonella Typhimurium (STm), which was subsequently stained with carboxyfluorescein succinimidyl ester. Upon culture at various febrile temperatures, RNA sequencing identified 18 temperature-independent pathways that were activated at 37–40 °C and responsible for cell death, PAMP receptors, and the synthesis of effector proteins, as well as eight high temperature-dependent pathways that were activated only at 38–40 °C and responsible for endocytosis, cell killing, and cell interactions. The FCM analysis indicated that when weighed against potentially much more severe side effects from 40 to 41 °C, reasonably high bactericidal activity was achieved at 38–39 °C in macrophages. Our findings provide essential knowledge about fever control treatment in terms of basic immune and metabolic pathways.