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Cell Host Microbe. 2008 May 15;3(5):331-8. doi: 10.1016/j.chom.2008.04.003.

Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.

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Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal.


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.

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