| First Author | Tran TM | Year | 2019 |
| Journal | Immunity | Volume | 51 |
| Issue | 4 | Pages | 750-765.e10 |
| PubMed ID | 31492649 | Mgi Jnum | J:305847 |
| Mgi Id | MGI:6706597 | Doi | 10.1016/j.immuni.2019.08.009 |
| Citation | Tran TM, et al. (2019) A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation. Immunity 51(4):750-765.e10 |
| abstractText | Immunity that controls parasitemia and inflammation during Plasmodium falciparum (Pf) malaria can be acquired with repeated infections. A limited understanding of this complex immune response impedes the development of vaccines and adjunctive therapies. We conducted a prospective systems biology study of children who differed in their ability to control parasitemia and fever following Pf infection. By integrating whole-blood transcriptomics, flow-cytometric analysis, and plasma cytokine and antibody profiles, we demonstrate that a pre-infection signature of B cell enrichment, upregulation of T helper type 1 (Th1) and Th2 cell-associated pathways, including interferon responses, and p53 activation associated with control of malarial fever and coordinated with Pf-specific immunoglobulin G (IgG) and Fc receptor activation to control parasitemia. Our hypothesis-generating approach identified host molecules that may contribute to differential clinical outcomes during Pf infection. As a proof of concept, we have shown that enhanced p53 expression in monocytes attenuated Plasmodium-induced inflammation and predicted protection from fever. |
