title: Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.
abstract: The clinically silent Plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. We report here that expression of heme oxygenase-1 (HO-1, encoded by Hmox1) is upregulated in the liver following infection by Plasmodium berghei and Plasmodium yoelii sporozoites. HO-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of HO-1, also increases parasite liver load. Conversely, mice lacking Hmox1 completely resolve the infection. In the absence of HO-1, the levels of inflammatory cytokines involved in the control of liver infection are increased. These findings suggest that, while stimulating inflammation, the liver stage of Plasmodium also induces HO-1 expression, which modulates the host inflammatory response, protecting the infected hepatocytes and promoting the liver stage of infection.
authors.affiliation: Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Epiphanio
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mikolajczak
authors.forename: Lígia A
authors.initials: LA
authors.lastname: Gonçalves
authors.forename: Ana
authors.initials: A
authors.lastname: Pamplona
authors.forename: Silvia
authors.initials: S
authors.lastname: Portugal
authors.forename: Sónia
authors.initials: S
authors.lastname: Albuquerque
authors.forename: Michael
authors.initials: M
authors.lastname: Goldberg
authors.forename: Sofia
authors.initials: S
authors.lastname: Rebelo
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Akin
authors.initials: A
authors.lastname: Akinc
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Vornlocher
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000469:parasitology; D054884:Host-Pathogen Interactions; D008099:Liver / Q000276:immunology* / Q000469:parasitology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D034101:Sporozoites / Q000276:immunology; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse