| First Author | Chora ÂF | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 3 | Pages | 592-605.e8 |
| PubMed ID | 36804959 | Mgi Jnum | J:340980 |
| Mgi Id | MGI:7448323 | Doi | 10.1016/j.immuni.2023.01.031 |
| Citation | Chora AF, et al. (2023) Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via gammadelta T cells and IL-17-promoted stress erythropoiesis. Immunity 56(3):592-605.e8 |
| abstractText | 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 Vgamma4(+) gammadelta T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing gammadelta 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 gammadelta T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals. |
