A novel model of asymptomatic plasmodium parasitemia that recapitulates elements of the human immune response to chronic infection

Mary F. Fontana, Alyssa Baccarella, Joshua F. Craft, Michelle J. Boyle, Tara I. McIntyre, Matthew Wood, Kurt S. Thorn, Chioma Anidi, Aqieda Bayat, Me Ree Chung, Rebecca Hamburger, Chris Y. Kim, Emily Pearman, Jennifer Pham, Jia J. Tang, Louis Boon, Moses R. Kamya, Grant Dorsey, Margaret E. Feeney, Charles C. Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection.

Original languageEnglish (US)
Article number0162132
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Plasmodium
Parasitemia
parasitemia
Immunity
immune response
Infection
infection
Dissection
T-cells
Malaria
Pathology
immunity
animal models
mice
Interleukin-10
Animals
Cells
Asymptomatic Infections
patents
interleukin-10

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A novel model of asymptomatic plasmodium parasitemia that recapitulates elements of the human immune response to chronic infection. / Fontana, Mary F.; Baccarella, Alyssa; Craft, Joshua F.; Boyle, Michelle J.; McIntyre, Tara I.; Wood, Matthew; Thorn, Kurt S.; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y.; Pearman, Emily; Pham, Jennifer; Tang, Jia J.; Boon, Louis; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.; Kim, Charles C.

In: PloS one, Vol. 11, No. 9, 0162132, 01.09.2016.

Research output: Contribution to journalArticle

Fontana, MF, Baccarella, A, Craft, JF, Boyle, MJ, McIntyre, TI, Wood, M, Thorn, KS, Anidi, C, Bayat, A, Chung, MR, Hamburger, R, Kim, CY, Pearman, E, Pham, J, Tang, JJ, Boon, L, Kamya, MR, Dorsey, G, Feeney, ME & Kim, CC 2016, 'A novel model of asymptomatic plasmodium parasitemia that recapitulates elements of the human immune response to chronic infection', PloS one, vol. 11, no. 9, 0162132. https://doi.org/10.1371/journal.pone.0162132
Fontana, Mary F. ; Baccarella, Alyssa ; Craft, Joshua F. ; Boyle, Michelle J. ; McIntyre, Tara I. ; Wood, Matthew ; Thorn, Kurt S. ; Anidi, Chioma ; Bayat, Aqieda ; Chung, Me Ree ; Hamburger, Rebecca ; Kim, Chris Y. ; Pearman, Emily ; Pham, Jennifer ; Tang, Jia J. ; Boon, Louis ; Kamya, Moses R. ; Dorsey, Grant ; Feeney, Margaret E. ; Kim, Charles C. / A novel model of asymptomatic plasmodium parasitemia that recapitulates elements of the human immune response to chronic infection. In: PloS one. 2016 ; Vol. 11, No. 9.
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