Invasive infection with Salmonella is a common complication in people with malaria. In Nature Medicine, Riley and colleagues show that loss of resistance to Salmonella is due to the hemolytic release of heme and the subsequent induction of heme oxygenase (HO-1), which is essential for tolerance to the cytotoxic effects of free heme during malaria. Progressive release of free heme and HO-1 impairs maturation of the oxidative-burst ability of granulocytes in the bone marrow and mobilizes functionally immature granulocytes in the peripheral circulation, which can phagocytose but cannot kill bacteria and thus provide a niche for the replication and dissemination of Salmonella. Inhibition of HO-1 restores normal development of the oxidative burst in maturing bone marrow granulocytes and resistance to Salmonella. These results indicate that resistance and tolerance mechanisms are pathogen specific and can diminish resistance to another pathogen.

Nat. Med. 18, 120–127 (2012)