Platelets as Immune Cells in Infectious Diseases

Cornelia Speth; Jürgen Löffler; Sven Krappmann; Cornelia Lass-Flörl; Günter Rambach


Future Microbiol. 2013;8(11):1431-1451. 

In This Article

Platelets in Parasite Infections

Although data are limited, there is no doubt that platelets also interact with parasites and play a substantial role in the antiparasitic immune defense. Activation of platelets is triggered by direct adhesion of the parasites to platelet receptors, in addition to other stimuli, such as increased levels of CRP.

After contact with parasites, platelets express defined immune receptors on their surface and secrete prestored cytokines and chemokines from their granules and thus also attract other immune cells such as macrophages, granulocytes and T cells.

Worm Infections

Schistosomiasis, which is considered by the WHO to be the second most socioeconomically devastating parasitic infection with hundreds of millions of infections worldwide, is caused by Schistosoma, a genus of trematodes.[192] Schistosoma eggs are passed through urine or feces to fresh water, where a larval stage (cercariae) of the parasite emerges that infects humans by directly penetrating their skin.

The relevance of the interaction between Schistosoma mansoni and platelets has been studied in vivo and in vitro.[193] Isolated platelets efficiently adhere and kill schistosomula (the migratory larval form) in vitro.[193,194] Furthermore, it could be shown that platelets acquired toxic properties towards Schistosoma when serum from infected individuals is present. The relevant humoral factor was shown to be IgE, which might bind to a Fc receptor for IgE on platelets. The transfer of platelets from immune to susceptible rats conferred protection towards a challenge infection by the parasite. When thrombocytopenic mice were infected by Schistosoma, worm burdens were significantly higher than in control mice with normal platelet numbers.[194]

The schistosomicidal activity of platelets seems to be regulated and enhanced by TNF-α and TNF-β. Damonneville et al. demonstrated that TNF induced the cytotoxic activity of platelets towards the larvae of S. mansoni in vitro.[195] Transfer of platelets prestimulated with TNF significantly protected rats from infection and reduced worm burden. Platelets can also affect Schistosoma indirectly via their effect on adhesion and migration of T cells, NK and B cells.[195]

The potency of platelet attack is reflected by the fact that Schistosoma evolved appropriate evasion mechanisms. First, mice infected percutaneously with cercariae develop a moderate thrombocytopenia. This thrombocytopenia may be a strategy that helps secondarily incoming parasites to evade host defense, similar to bacteria-induced or virus-induced platelet loss. Second, S. mansoni express an ATP-diphosphohydrolase localized on the external surface. This enzyme hydrolyzes nucleoside tri- and di-phosphates, for example, the platelet-activating ADP. By this mechanism S. mansoni is suggested to inhibit platelet aggregation and thus escape from platelet-associated immune mechanisms.[196,197]

Another clinically relevant worm is Echinococcus granulosus, a cestode that parasitizes the small intestine of canids as an adult, but has humans as intermediate hosts, where it causes cystic echinococcosis. In canidae, E. granulosus produces eggs that are passed with the dog's feces. Intermediate hosts ingest dog feces by smear infections, and the Echinococcus eggs form larvae, which travel through the blood and form hydatid cysts in various tissues. There are reports that platelet activation is increased in the blood of echinococcosis patients, as demonstrated by increased CD62P exposition, elevated concentrations of platelet granule-derived β-thromboglobulin and PF-4, and high amounts of microparticles.[198–200] Platelet activation might be mediated either by direct contact with echinococcal surface structures or by binding to IgE or IgG antibodies coating the parasites; activation by the inflammatory reaction can also be postulated. In vitro experiments demonstrated that platelets can exert cytotoxic activity against antibody-coated parasites.[201]

Platelets are also able to confer resistance against larvae of Taenia taeniaeformis. The transfer of platelets from donor mice that were immune against T. taeniaeformis protected susceptible-recipient animals against a challenge infection with this parasite.[202]


Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. Cats are the main source of infection for humans, where infection symptoms range from mild to neurologic diseases. Congenital transmission might lead to chorioretinitis, hearing loss or mental retardation in the child.[203]

T. gondii tachyzoites are able to activate platelets during primary infection as well as reactivated toxoplasmosis. As a consequence, platelets exert a strong antiparasitic activity and, after preincubation with platelets in vitro, Toxoplasma is unable to infect mice.[204,205] This toxic activity might be mediated by thromboxane, mainly formed by platelets and released after activation. Thromboxane disturbs the T. gondii surface thus decreasing its viability.[206] Furthermore, platelet-derived PDGF could contribute to the antiparasitic effect since it inhibits intracellular growth of T. gondii; the cyclooxygenase cycle of fibroblasts and increased IL-6 production might be involved in this mechanism.[204]


Malaria is caused by parasites of the genus Plasmodium, the most lethal of which, Plasmodium falciparum, predominates in Africa. Infection by this pathogen results in a febrile disease with intermittent episodes of fever and severe courses may lead to death. According to the CDC, an estimated 219 million malaria cases occurred worldwide in 2010, out of which 660,000 individuals died as a result of infection.

Plasmodium can interact with different receptors on human platelets. CD36 (GPIV) mediates attachment of P. falciparum on erythrocytes and is also expressed on platelets.[207] Furthermore, it is thought to be the key platelet receptor in the interaction with infected erythrocytes.[208] Other molecules such as CD31 (PECAM-1) and the complement receptor gC1qR/HABP1/p32 might contribute to interaction with Plasmodium or Plasmodium-infected erythrocytes.[208]

Plasmodium infection has also been correlated with platelet activation in various studies. Increased CD62P levels and enhanced levels of PF-3 were measured in patients with malaria.[209–211] Animal models support the hypothesis of Plasmodium-driven platelet activation and reveal an increase in CD62P levels, microparticle formation and thromboxane release.[208]

This process of platelet stimulation can explain the thrombocytopenia commonly found in malaria.[212,213] Discussions of the consequences of platelet loss are very controversial. On one hand, it might be beneficial for the parasite, at least in early stages of infection, since platelets efficiently bind to infected erythrocytes and kill the intraerythrocytic plasmodia; platelet-deficient mice were more susceptible to death by Plasmodium infection.[214] This beneficial aspect is underlined by the fact that the extent of thrombocytopenia is a predictor for the outcome and severity of disease,[215] and low platelet concentrations, correlate with increased parasite density.[216] Similar to HIV, the platelet-derived chemokine PF-4 plays a central role for antimicrobial killing. PF4 rapidly accumulates within infected erythrocytes and kills intracellular malaria parasites by selectively lysing the parasite digestive vacuole.[52,217] Conversely, some hints indicate that platelets are involved in the pathogenesis of cerebral malaria in the late stages of infection. In an experimental mouse model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve the outcome of infection. Platelet accumulation also occurs in the microvasculature of patients with cerebral malaria and thus may contribute to pathogenesis.[218] Platelets also potentiate brain endothelial alterations induced by P. falciparum.[219] In this case of cerebral malaria, thrombocytopenia may provide a protective reaction of the host through reduction of platelet-mediated clumping of infected erythrocytes.[220]