Distinct roles of IL-27 produced by macrophages and dendritic cells in shaping the immune response against Plasmodium parasites

To determine cell types that produce IL-27, IL-27 reporter IL27p28-Venus mice was generated and monitored its expression. It was detected that both dendritic cells (DCs) and macrophages express IL-27 during acute phase of the infection with P.chabaudi. DCs are the major antigen-presenting cells for the activation of adaptive immunity, and macrophages are critical effector cells to control parasitemia. Therefore, it was speculated that IL-27 produced by these cells have differential roles in the regulation of immune responses during Plasmodium infection. To this end, the study generated mice lacking IL-27 in DCs (IL27p28fl/flCD11c-Cre) or in macrophages (IL27p28fl/flLysM-Cre) and compared the response of these mice to the infection with P. chabaudi. Mice lacking IL-27 in DCs showed delay in the clearance of parasitemia than that in control mice (IL27p28fl/fl) during the acute phase of the infection, while those in macrophages exhibited earlier parasitemia peak and earlier clearance. Results suggested that the frequencies of activated CD4+ T cells (CD11ahiCD49dhi) and IFN-γ production in the spleen in response to malaria antigen were higher in mice lacking IL-27 in DCs than those in mice lacking IL-27 in macrophages. It was also found that malaria antigen specific antibody IgG1 and Ig2b were higher mice lacking IL-27 in DCs than those in mice lacking IL-27 in macrophages. These results suggest that IL-27 produced by DC and macrophages play qualitatively differential roles in the immune responses against Plasmodium infection.

Project details

Basic Science

Apr 2020 — Mar 2024

$36,463

Japan