Trypanosome resistance to human innate immunity: targeting Achilles¡¯ heel

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• 作者：Natalie A. Stephens¹ ; Rudo Kieft¹ ; Annette MacLeod² ; Stephen L. Hajduk¹ ; ^{shajduk@bmb.uga.edu}
• 关键词：African trypanosomes ; innate immunity ; high density lipoproteins ; haptoglobin ; apolipoprotein L-1 ; haptoglobin related protein ; serum resistance associated protein ; trypanosome lytic factor
• 刊名：Trends in Parasitology
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：28
• 期：12
• 页码：539-545
• 全文大小：608 K

文摘

Trypanosome lytic factors (TLFs) are powerful, naturally occurring toxins in humans that provide sterile protection against infection by several African trypanosomes. These trypanocidal complexes predominantly enter the parasite by binding to the trypanosome haptoglobin/hemoglobin receptor (HpHbR), trafficking to the lysosome, causing membrane damage and, ultimately, cell lysis. Despite TLF-mediated immunity, the parasites that cause human African Trypanosomiasis (HAT), Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, have developed independent mechanisms of resistance to TLF killing. In this review we describe the parasite defenses that allow trypanosome infections of humans and discuss how targeting these apparent strengths of the parasite may reveal their Achilles¡¯ heel, leading to new approaches in the treatment of HAT.