Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.
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.
Epiphanio
Sabrina
S
Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Mikolajczak
Sebastian A
SA
Gonçalves
Lígia A
LA
Pamplona
Ana
A
Portugal
Silvia
S
Albuquerque
Sónia
S
Goldberg
Michael
M
Rebelo
Sofia
S
Anderson
Daniel G
DG
Akinc
Akin
A
Vornlocher
Hans-Peter
HP
Kappe
Stefan H I
SH
Soares
Miguel P
MP
Mota
Maria M
MM
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
D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse