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

被引：110

作者：

Epiphanio, Sabrina ^{[1
,2
]}

Mikolajczak, Sebastian A. ^{[7
]}

Goncalves, Ligia A. ^{[2
]}

Pamplona, Ana ^{[1
,2
]}

Portugal, Silvia ^{[1
,2
]}

Albuquerque, Sonia ^{[1
,2
]}

Goldberg, Michael ^{[3
]}

Rebelo, Sofia ^{[2
]}

Anderson, Daniel G. ^{[4
]}

Akinc, Akin ^{[5
]}

Vornlocher, Hans-Peter ^{[6
]}

Kappe, Stefan H. I. ^{[7
]}

Soares, Miguel P. ^{[2
]}

Mota, Maria M. ^{[1
,2
]}

机构：

[1] Univ Lisbon, Unidade Malaria, Inst Mol Med, P-1649028 Lisbon, Portugal

[2] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal

[3] MIT, Dept Chem, Cambridge, MA 02139 USA

[4] David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[5] Alnylam Pharmaceut, Cambridge, MA 02142 USA

[6] Roche Kulmbach GmbH, D-95236 Kulmbach, Germany

[7] Seattle Biomed Res Inst, Seattle, WA 98109 USA

来源：

CELL HOST & MICROBE | 2008年 / 3卷 / 05期

关键词：

D O I：

10.1016/j.chom.2008.04.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：331 / 338

页数：8

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