Malaria is still the most important parasitic infectious disease in the world, caused by malaria parasite Plasmodium, which proliferates in host erythrocytes, digests hemoglobin and generates the bio-crystal hemozoin (HZ) from haemoglobin heme. Every 48 h, parasites re-invade new erythrocytes and HZ interacts with immune cells after being released into the bloodstream. In this study we show that host fibrinogen from human plasma is stably bound to HZ and rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin receptors. The following avid phagocytosis of indigestible HZ resulted in persistence and accumulation of HZ inside phagocytes. Thus, naturally occurring binding of fibrinogen to the HZ crystal assigns properties of a strong immune activator to HZ. Ref: Barrera V, Skorokhod OA, Baci D, Gremo G, Arese P, Schwarzer E. Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action. Blood. 2011 May 26;117(21):5674-82. doi: 10.1182/blood-2010-10-312413. Epub 2011 Apr 1. PMID: 21460246.
Biological activity of malarial nanocrystal hemozoin is due to host fibrinogen: a newly described mechanism of innate immune response to malaria
Skorokhod O.
;Schwarzer E.
2021-01-01
Abstract
Malaria is still the most important parasitic infectious disease in the world, caused by malaria parasite Plasmodium, which proliferates in host erythrocytes, digests hemoglobin and generates the bio-crystal hemozoin (HZ) from haemoglobin heme. Every 48 h, parasites re-invade new erythrocytes and HZ interacts with immune cells after being released into the bloodstream. In this study we show that host fibrinogen from human plasma is stably bound to HZ and rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin receptors. The following avid phagocytosis of indigestible HZ resulted in persistence and accumulation of HZ inside phagocytes. Thus, naturally occurring binding of fibrinogen to the HZ crystal assigns properties of a strong immune activator to HZ. Ref: Barrera V, Skorokhod OA, Baci D, Gremo G, Arese P, Schwarzer E. Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action. Blood. 2011 May 26;117(21):5674-82. doi: 10.1182/blood-2010-10-312413. Epub 2011 Apr 1. PMID: 21460246.
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