Interleukin 22 (IL-22) protects hosts against microbial infection at barrier tissues. In Science Immmunology, Sakamoto et al. show that IL-22 also induces host resistance to systemic infection by pathogenic gut bacteria. Intravenous infection with Citrobacter rodentium or Escherichia coli induces IL-22 that induces liver production of acute-phase response proteins, including the heme scavenger hemopexin (HPX). Il22−/− or Hpx−/− mice are unable to control bacterial proliferation in blood and succumb to infection by pathogens that express hemolysins or other virulence proteins that liberate host heme complexes. Administration of HPX rescues Il22−/− mice from death after bacterial blood infection, which suggests that sequestration of heme is sufficient to retard bacterial growth until other immune responses develop to control the infection.

Sci. Immunol. 2, eaai8371 (2017)