AUTHOR=Wrande Marie , Vestö Kim , Puiac Banesaru Speranta , Anwar Naeem , Nordfjell Johan , Liu Lifeng , McInerney Gerald M. , Rhen Mikael TITLE=Replication of Salmonella enterica serovar Typhimurium in RAW264.7 Phagocytes Correlates With Hypoxia and Lack of iNOS Expression JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.537782 DOI=10.3389/fcimb.2020.537782 ISSN=2235-2988 ABSTRACT=

Salmonella infection associates with tissue hypoxia, while inducible nitric oxide synthase (iNOS), relying for its activity on molecular oxygen, stands as a central host defence measure in murine salmonellosis. Here, we have detailed hypoxia and iNOS responses of murine macrophage-like RAW264.7 cells upon infection with Salmonella enterica serovar Typhimurium. We noted that only a proportion of the infected RAW264.7 cells became hypoxic or expressed iNOS. Heavily infected cells became hypoxic, while in parallel such cells tended not to express iNOS. While a proportion of the infected RAW264.7 cells revealed shutdown of protein synthesis, this was only detectable after 12 h post infection and after iNOS expression was induced in the cell culture. Our data implicate an intrinsic heterogeneity with regard to hypoxia and iNOS expression in a cell culture-based infection setting.