RT Journal Article
SR Electronic
T1 An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4<sup>+</sup> T Cell Response by a Whole-Killed Blood-Stage Vaccine
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 178
OP 186
DO 10.4049/jimmunol.1201190
VO 191
IS 1
A1 Liu, Taiping
A1 Xu, Guilian
A1 Guo, Bo
A1 Fu, Yong
A1 Qiu, Yuan
A1 Ding, Yan
A1 Zheng, Hong
A1 Fu, Xiaolan
A1 Wu, Yuzhang
A1 Xu, Wenyue
YR 2013
UL http://www.jimmunol.org/content/191/1/178.abstract
AB The protective immunity induced by the whole-killed parasite vaccine against malarial blood-stage infection is dependent on the CD4+ T cell response. However, the mechanism underlying this robust CD4+ T cell response elicited by the whole-killed parasite vaccine is still largely unknown. In this study, we observe that immunization with Plasmodium yoelii–parasitized RBC lysate activates complement C5 and generates C5a. However, the protective efficacy against P. yoelii 17XL challenge is considerably reduced, and the malaria-specific CD4+ T cell activation and memory T cell differentiation are largely suppressed in the C5aR-deficient (C5aR−/−) mice. An adoptive transfer assay demonstrates that the reduced protection of C5aR−/− mice is closely associated with the severely impaired CD4+ T cell response. This is further confirmed by the fact that administration of C5aR antagonist significantly reduces the protective efficacy of the immunized B cell–deficient mice. Further study indicates that the defective CD4+ T cell response in C5aR−/− mice is unlikely involved in the expansion of CD4+CD25+Foxp3+ T cells, but strongly linked to a defect in dendritic cell (DC) maturation and the ability to allostimulate CD4+ T cells. These results demonstrate that C5aR signaling is essential for the optimal induction of the malaria-specific CD4+ T cell response by the whole-killed parasite vaccine through modulation of DCs function, which provides us with new clues to design an effective blood-stage subunit vaccine and helps us to understand the mechanism by which the T cell response is regulated by the complement system.