A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation

Tuan M. Tran, Rajan Guha, Silvia Portugal, Jeff Skinner, Aissata Ongoiba, Jyoti Bhardwaj, Marcus Jones, Jacqueline Moebius, Pratap Venepally, Safiatou Doumbo, Elizabeth A. DeRiso, Shanping Li, Kamalakannan Vijayan, Sarah L. Anzick, Geoffrey T. Hart, Elise M. O’Connell, Ogobara K. Doumbo, Alexis Kaushansky, Galit Alter, Phillip L. FelgnerHernan Lorenzi, Kassoum Kayentao, Boubacar Traore, Ewen F. Kirkness, Peter D. Crompton

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish (US)
Pages (from-to)750
JournalImmunity
Volume51
Issue number4
DOIs
StatePublished - Oct 15 2019

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Parasitemia
Plasmodium falciparum
Malaria
Inflammation
Fever
IgG Receptors
Active Immunotherapy
Th2 Cells
Th1 Cells
Systems Biology
Plasmodium
Fc Receptors
Falciparum Malaria
Infection
Antigen-Antibody Complex
Interferons
Monocytes
Immunity
B-Lymphocytes
Up-Regulation

Cite this

Tran, T. M., Guha, R., Portugal, S., Skinner, J., Ongoiba, A., Bhardwaj, J., ... Crompton, P. D. (2019). A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation. Immunity, 51(4), 750. https://doi.org/10.1016/j.immuni.2019.08.009

A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation. / Tran, Tuan M.; Guha, Rajan; Portugal, Silvia; Skinner, Jeff; Ongoiba, Aissata; Bhardwaj, Jyoti; Jones, Marcus; Moebius, Jacqueline; Venepally, Pratap; Doumbo, Safiatou; DeRiso, Elizabeth A.; Li, Shanping; Vijayan, Kamalakannan; Anzick, Sarah L.; Hart, Geoffrey T.; O’Connell, Elise M.; Doumbo, Ogobara K.; Kaushansky, Alexis; Alter, Galit; Felgner, Phillip L.; Lorenzi, Hernan; Kayentao, Kassoum; Traore, Boubacar; Kirkness, Ewen F.; Crompton, Peter D.

In: Immunity, Vol. 51, No. 4, 15.10.2019, p. 750.

Research output: Contribution to journalArticle

Tran, TM, Guha, R, Portugal, S, Skinner, J, Ongoiba, A, Bhardwaj, J, Jones, M, Moebius, J, Venepally, P, Doumbo, S, DeRiso, EA, Li, S, Vijayan, K, Anzick, SL, Hart, GT, O’Connell, EM, Doumbo, OK, Kaushansky, A, Alter, G, Felgner, PL, Lorenzi, H, Kayentao, K, Traore, B, Kirkness, EF & Crompton, PD 2019, 'A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation', Immunity, vol. 51, no. 4, pp. 750. https://doi.org/10.1016/j.immuni.2019.08.009
Tran, Tuan M. ; Guha, Rajan ; Portugal, Silvia ; Skinner, Jeff ; Ongoiba, Aissata ; Bhardwaj, Jyoti ; Jones, Marcus ; Moebius, Jacqueline ; Venepally, Pratap ; Doumbo, Safiatou ; DeRiso, Elizabeth A. ; Li, Shanping ; Vijayan, Kamalakannan ; Anzick, Sarah L. ; Hart, Geoffrey T. ; O’Connell, Elise M. ; Doumbo, Ogobara K. ; Kaushansky, Alexis ; Alter, Galit ; Felgner, Phillip L. ; Lorenzi, Hernan ; Kayentao, Kassoum ; Traore, Boubacar ; Kirkness, Ewen F. ; Crompton, Peter D. / A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation. In: Immunity. 2019 ; Vol. 51, No. 4. pp. 750.
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AU - Guha, Rajan

AU - Portugal, Silvia

AU - Skinner, Jeff

AU - Ongoiba, Aissata

AU - Bhardwaj, Jyoti

AU - Jones, Marcus

AU - Moebius, Jacqueline

AU - Venepally, Pratap

AU - Doumbo, Safiatou

AU - DeRiso, Elizabeth A.

AU - Li, Shanping

AU - Vijayan, Kamalakannan

AU - Anzick, Sarah L.

AU - Hart, Geoffrey T.

AU - O’Connell, Elise M.

AU - Doumbo, Ogobara K.

AU - Kaushansky, Alexis

AU - Alter, Galit

AU - Felgner, Phillip L.

AU - Lorenzi, Hernan

AU - Kayentao, Kassoum

AU - Traore, Boubacar

AU - Kirkness, Ewen F.

AU - Crompton, Peter D.

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