The role of IL-1β in protection from Salmonella infection

The foodborne pathogen Salmonella typhimurium (S. Tm) has evolved to manipulate the
relationship between the host and its microbiota. By triggering an inflammatory response, S. Tm
alters the intestinal environment to support its growth and the killing of its competitors, the
microbiota. Specifically, S. Tm infection leads to neutrophil recruitment to the colon, which kills
short-chain fatty acids (SCFA)-producing commensal bacteria, forcing the host to switch energy
production from β- oxidation of SCFA, to glycolysis. This metabolic manipulation of the host by
S. Tm leads to oxidation of the gut, as glycolysis does not consume oxygen, further harming
resident microbes which are mostly obligate anaerobes. Yet exactly how S. Tm manipulates the
host immune system to trigger this cascade is not known. We found that mice lacking the
proinflammatory cytokine interleukin 1β (IL-1β -/- ) fail to recruit neutrophils to the gut during S. Tm
infection. Unexpectedly, this immune deficiency protected IL-1β -/- mice from infection, reducing
mortality, tissue damage, and impeding S. Tm expansion. We also found that infected IL-1β -/-
mice did not carry out a transcriptional program that indicates metabolic switching to glycolysis.
Indeed, hypoxia levels in infected IL-1β -/- were significantly higher than infected wild type mice.
This implies that IL-1β is a central component of host manipulation by S. Tm which allows the
pathogen to outcompete the microbiota.