A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria

作者：Sun Tiffany; Holowka Thomas; Song Yan; Zierow Swen; Leng Lin; Chen Yibang; Xiong Huabao; Griffith Jason; Nouraie Mehdi; Thuma Philip E; Lolis Elias; Janse Chris J; Gordeuk Victor R; Augustijn Kevin; Bucala Richard^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(31): E2117-E2126.

DOI：10.1073/pnas.1206573109

• vaccine
• immune evasion

The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.

• 出版日期2012-7-31