γδ T Cell Therapy Development for Plasmodium Infections and Human Malaria

Human Malaria and Immunity

Plasmodium is a category of single-celled eukaryotic microorganisms, which specially parasitize vertebrates and insects. Human malaria, one of the most widespread infections with high morbidity and mortality, is caused by Plasmodium spp infections that are commonly spread by an infected mosquito.

Once Plasmodium or sporozoites enter the human body, the immune system mounts a series of protective immune responses. Physical barriers function as the first line to defend the host against Plasmodium infection. B lymphocytes produce antibodies to block them from invading liver cells and erythrocytes, which also neutralize and lyse parasites through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity. Furthermore, by recognizing parasite, producing cytokine (e.g., interferon-γ), and activating other immunocytes (e.g., macrophages), T lymphocytes provide effective protection for the host from malaria.

Fig.1 Immune response against malaria pre-erythrocytic stages (sporozoites and liver stages). (Mueller, 2013)

Role of γδ T Cell in Human Malaria

During Plasmodium infections, γδ T cells rapidly proliferate and expand, accounting for up to 30-40% of peripheral T cells and exerting important protective immunity against malaria.

• Plasmodium recognition

γδ T cell, especially Vγ9Vδ2 T cell, has been hypothesized to recognize and respond to phosphoantigens secreted by Plasmodium-infected red blood cell. For the Plasmodium sporozoite stage, γδ T cells are directly activated by antigen uniquely expressed by the parasite.

• Cytotoxic effect and cytokine secretion

The activated γδ T cells produce large amounts of cytokine, mainly interferon-γ (IFN-γ), in response to malaria infection, which has a cytotoxic effect on Plasmodium sporozoite in infected hepatocytes, or activates phagocytes and macrophages to eliminate parasites in blood-stage through ADCC. Other cytokines and cytotoxic molecules (i.e., granulysin, interleukins) produced by activated γδ T cells also involve the inhibition of malaria infection.

• Immunological memory to malaria

For the initial malaria infection, γδ T cells significantly expanded in the later stage of infection. The frequency of the expression of effector memory surface markers on the γδ T cell was elevated and the response to Plasmodium stimulation was enhanced, both of which lasted for more than one year.

Fig.2 Model for Vγ9Vδ2 γδ T cell response to Plasmodium falciparum. (Dantzler, 2018)

Development Service for Malaria Therapy by γδ T Cell at Creative Biolabs

Plasmodium infection or malaria has been one of the most important infectious diseases in the world. γδ T cells, a small group of defenders in the immune system, may be a promising approach for the prevention and treatment of malaria. Creative Biolabs is a recognized service provider that focuses on γδ T cell therapy development for several years. Based on integrated platforms and extensive experience, our scientists provide comprehensive custom γδ T cell therapy development services for malaria treatment, as well as other related diseases, such as tumors, autoimmune disorders, neurological diseases, etc.

Please feel free to contact us and our experienced technicians will provide as much support as we can.

References

1. Mueller, I., et al. Natural acquisition of immunity to Plasmodium vivax: epidemiological observations and potential targets. Advances in Parasitology. 2013, 81: 77-131.
2. Dantzler, K.W., Jagannathan, P. γδ T Cells in Antimalarial Immunity: New Insights Into Their Diverse Functions in Protection and Tolerance. Frontiers in Immunology. 2018, 9: 2445.