1. γδ T cell-mediated activation of cDC1 orchestrates CD4 + Th1 cell priming in malaria.
- Author
-
Ibraheem Y, Bayarsaikhan G, Macalinao ML, Kimura K, Yui K, Aoshi T, and Inoue SI
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Receptors, CXCR3 metabolism, Receptors, Antigen, T-Cell, gamma-delta metabolism, Receptors, Antigen, T-Cell, gamma-delta immunology, Receptors, CCR7 metabolism, Receptors, CCR7 immunology, Signal Transduction, Spleen immunology, Cell Differentiation immunology, Female, Th1 Cells immunology, Dendritic Cells immunology, Dendritic Cells metabolism, Lymphocyte Activation immunology, Malaria immunology, Malaria parasitology
- Abstract
γδ T cells facilitate the CD4
+ T helper 1 (Th1) cell response against Plasmodium infection by activating conventional dendritic cells (cDCs), although the underlying mechanism remains elusive. Our study revealed that γδ T cells promote the complete maturation and production of interleukin-12 and CXCR3-ligands specifically in type 1 cDCs (cDC1), with minimal impact on cDC2 and monocyte derived DCs (Mo-DCs). During the initial infection phase, γδ T cell activation and temporal accumulation in the splenic white pulp, alongside cDC1, occur via CCR7-signaling. Furthermore, cDC1/γδ T cell interactions in the white pulp are amplified through CXCR3 signaling in γδ T cells, optimizing Th1 cell priming by cDC1. We also demonstrated how transitional Th1 cells arise in the white pulp before establishing their presence in the red pulp as fully differentiated Th1 cells. Additionally, we elucidate the reciprocal activation between γδ T cells and cDC1s. These findings suggest that Th1 cell priming is orchestrated by this reciprocal activation in the splenic white pulp during the early phase of blood-stage Plasmodium infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ibraheem, Bayarsaikhan, Macalinao, Kimura, Yui, Aoshi and Inoue.)- Published
- 2024
- Full Text
- View/download PDF