Malaria impairs resistance to Salmonella...
Aubrey J Cunnington, J Brian de Souza, Michael Walther & Eleanor M Riley
In sub-Saharan Africa, invasive nontyphoid Salmonella (NTS) infection is a common and often fatal complication of Plasmodium
falciparum infection. Induction of heme oxygenase-1 (HO-1) mediates tolerance to the cytotoxic effects of heme during malarial
hemolysis but might impair resistance to NTS by limiting production of bactericidal reactive oxygen species.
We show that co-infection of mice with Plasmodium yoelii 17XNL (Py17XNL) and Salmonella enterica serovar Typhimurium 12023 (Salmonella
typhimurium) causes acute, fatal bacteremia with high bacterial load, features reproduced by phenylhydrazine-induced hemolysis
or hemin administration. S. typhimurium localized predominantly in granulocytes. Py17XNL, phenylhydrazine and hemin caused
premature mobilization of granulocytes from bone marrow with a quantitative defect in the oxidative burst. Inhibition of HO by
tin protoporphyrin abrogated the impairment of resistance to S. typhimurium by hemolysis. Thus, a mechanism of tolerance to
one infection, malaria, impairs resistance to another, NTS. Furthermore, HO inhibitors may be useful adjunctive therapy for NTS
infection in the context of hemolysis.
VOLUME 18 | NUMBER 1 | JANUARY 2012 nature medicine
