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Host response

PF4 — platelets' poison

Nature Reviews Microbiology volume 11, pages 72–73 (2013)Cite this article

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PF4 is a human defence peptide (HDP) that has antimicrobial activity towards many pathogenic bacteria and fungi. As PF4 is released from platelets following stimulation with Plasmodium falciparum-infected erythrocytes, McMorran et al. reasoned that it might also have a role in killing the parasite. They found that PF4 colocalized with P. falciparum-infected erythrocytes but not with non-infected cells. Importantly, PF4 colocalized with dead intracellular P. falciparum within infected erythrocytes incubated with platelets. Consistent with this, treatment of erythrocytes with PF4-specific antibodies blocked the parasite-killing activity of platelets, confirming that PF4 is the effector molecule.

In a second study, Love et al. postulated that because HDPs have important roles in innate immunity, it is likely that an HDP is responsible for killing P. falciparum. During a screen for candidate HDPs, they observed that PF4 killed P. falciparum with high potency and without affecting the host erythrocyte. Moreover, platelets from wild-type mice or mice overexpressing PF4 showed high levels of P. falciparum killing in vitro, whereas those from PF4-knockout mice showed no killing activity. Interestingly, Love et al. observed that the 12-residue carboxyl terminus of PF4 was sufficient to kill P. falciparum in vitro.

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ORIGINAL RESEARCH PAPERS

  1. McMorran, B. J. et al. Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. Science 338, 1348–1351 (2012)

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  2. Love, M. S. et al. Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials. Cell Host Microbe 12, 815–823 (2012)

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  1. Rachel David
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David, R. PF4 — platelets' poison. Nat Rev Microbiol 11, 72–73 (2013). https://doi.org/10.1038/nrmicro2955

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