Item Details

title

Investigating The Role of Exogenous Metabolites on Erythroid Cells in Malarial Anemia

author

Binns, Heather Colvin

abstract

Malarial anemia is the most reported clinical complication of human falciparum malaria. Pathogenesis of malarial anemia is a multifactorial process resulting from a combination of obligatory lysis of infected red blood cells, a vast loss of uninfected red blood cells, and dysregulated erythropoiesis. Variability in malarial anemia disease severity among individuals suggests host environment could influence disease dynamics. The blood plasma metabolic environment is distinctly altered during acute malaria, as reviewed in Chapter II, suggesting that plasma metabolites may be a factor that contributes to variation in disease severity. Here, we focus on exogenous metabolites and their impact on erythroid cells in the context of malarial anemia. In this body of work, we first explore the role of exogenous amino acids on uninfected (bystander) red blood cells in malaria. We find that the environment of Plasmodium falciparum, the causative agent for human falciparum malaria, induces oxidative stress in red blood cells from healthy participants, a likely mechanism involved in the malarial bystander effect. We further demonstrate that amino acid supplementation confers intrinsic protection to bystander RBCs, prior to oxidative stress exposure, suggesting a therapeutic role for amino acid supplementation in malarial anemia. Next, we investigate the impact of 4-hydroxynonenal, a malarial metabolite, on erythroblast differentiation. We report that HNE partially inhibits erythroblast cell growth. Lastly, we utilize metabolomics data collected in a previously published longitudinal malaria infection study to identify plasma metabolites significantly altered with respect to hemoglobin levels in vivo. We find that plasma carnitine levels are inversely associated with anemia status during a longitudinal malaria infection. Taken together, these studies highlight the importance of the host metabolic environment on erythroid cells and in the pathogenesis of malarial anemia.

subject

anemia

erythroblast

malaria

oxidative stress

Plasmodium falciparum

red blood cell

contributor

Cordy, Regina J (advisor)

Ornelles, David A (committee member)

Furdui, Cristina M (committee member)

Kim-Shapiro, Daniel B (committee member)

Lyles, Douglas S (committee member)

Pease, James B (committee member)

date

2023-07-25T17:48:43Z (accessioned)

2023 (issued)

degree

Microbiology & Immunology (discipline)

embargo

2025-06-06 (terms)

2025-06-06 (liftdate)

identifier

http://hdl.handle.net/10339/102267 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation