A carregar...
Projeto de investigação
Sem título
Financiador
Autores
Publicações
Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis
Publication . Chora, Ângelo Ferreira; Marques, Sofia; Lisboa Gonçalves, Joana; Lima, Priscila; Gomes Da Costa, Daniel; Fernandez-Ruiz, Daniel; Marreiros, Maria Inês; Ruivo, Pedro; Carvalho, Tânia; Ribeiro, Ruy M.; Serre, Karine; Heath, William R.; Silva-Santos, Bruno; Tate, Ann T.; Mota, Maria M.
Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medullary erythropoiesis and concomitant reticulocytosis, which protected mice from lethal experimental cerebral malaria (ECM). Adoptive transfer of erythroid precursors could rescue mice from ECM. Modeling of γδ T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals.
The malaria parasite has an intrinsic clock
Publication . Rijo-Ferreira, Filipa; Acosta-Rodriguez, Victoria A.; Abel, John H.; Kornblum, Izabela; Bento, Inês; Kilaru, Gokhul; Klerman, Elizabeth B.; Mota, Maria M.; Takahashi, Joseph S.
Malarial rhythmic fevers are the consequence of the synchronous bursting of red blood cells (RBCs) on completion of the malaria parasite asexual cell cycle. Here, we hypothesized that an intrinsic clock in the parasite Plasmodium chabaudi underlies the 24-hour-based rhythms of RBC bursting in mice. We show that parasite rhythms are flexible and lengthen to match the rhythms of hosts with long circadian periods. We also show that malaria rhythms persist even when host food intake is evenly spread across 24 hours, suggesting that host feeding cues are not required for synchrony. Moreover, we find that the parasite population remains synchronous and rhythmic even in an arrhythmic clock mutant host. Thus, we propose that parasite rhythms are generated by the parasite, possibly to anticipate its circadian environment.
Unidades organizacionais
Descrição
Palavras-chave
Contribuidores
Financiadores
Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
PTDC/MED-IMU/28664/2017