Enhancement of Dendritic Cell Activation Via CD40 Ligand-expressing γδ T Cells is Responsible for Protective Immunity to Plasmodium Parasites
Overview
Authors
Affiliations
Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell-deficient (TCRδ-KO) mice and control wild-type mice with Plasmodium berghei XAT, which is a nonlethal strain. Although infected red blood cells were eliminated within 30 d after infection, TCRδ-KO mice could not clear the infected red blood cells, showed high parasitemia, and eventually died. Therefore, γδ T cells are essential for clearance of the parasites. Here, we found that γδ T cells play a key role in dendritic cell activation after Plasmodium infection. On day 5 postinfection, γδ T cells produced IFN-γ and expressed CD40 ligand during dendritic cell activation. These results suggest that γδ T cells enhance dendritic cell activation via IFN-γ and CD40 ligand-CD40 signaling. This hypothesis is supported strongly by the fact that in vivo induction of CD40 signaling prevented the death of TCRδ-KO mice after infection with P. berghei XAT. This study improves our understanding of protective immunity against malaria and provides insights into γδ T-cell-mediated protective immunity against various infectious diseases.
γδ T cell-mediated activation of cDC1 orchestrates CD4 Th1 cell priming in malaria.
Ibraheem Y, Bayarsaikhan G, Macalinao M, Kimura K, Yui K, Aoshi T Front Immunol. 2024; 15:1426316.
PMID: 39211036 PMC: 11357926. DOI: 10.3389/fimmu.2024.1426316.
A landscape review of malaria vaccine candidates in the pipeline.
Tajudeen Y, Oladipo H, Yusuff S, Abimbola S, Abdulkadir M, Oladunjoye I Trop Dis Travel Med Vaccines. 2024; 10(1):19.
PMID: 39085983 PMC: 11293096. DOI: 10.1186/s40794-024-00222-3.
Sestan M, Mikasinovic S, Benic A, Wueest S, Dimitropoulos C, Mladenic K Nat Immunol. 2024; 25(6):981-993.
PMID: 38811816 DOI: 10.1038/s41590-024-01848-3.
Harit K, Bhattacharjee R, Matuschewski K, Becker J, Kalinke U, Schluter D Cell Death Dis. 2023; 14(7):480.
PMID: 37516734 PMC: 10387084. DOI: 10.1038/s41419-023-06014-5.
Properties and Roles of γδT Cells in NSM Infected C57BL/6 Mice.
Xie H, Xie S, Wang M, Wei H, Huang H, Xie A Front Cell Infect Microbiol. 2022; 11:788546.
PMID: 35127555 PMC: 8811364. DOI: 10.3389/fcimb.2021.788546.