Journal article
In vivo CD8+ T cell dynamics in the liver of Plasmodium yoelii immunized and infected mice
PloS one, Vol.8(8), pp.e70842-e70842
2013
DOI: 10.1371/journal.pone.0070842
PMCID: PMC3743839
PMID: 23967119
Abstract
Plasmodium falciparum malaria remains one of the most serious health problems globally and a protective malaria vaccine is desperately needed. Vaccination with attenuated parasites elicits multiple cellular effector mechanisms that lead to Plasmodium liver stage elimination. While granule-mediated cytotoxicity requires contact between CD8+ effector T cells and infected hepatocytes, cytokine secretion should allow parasite killing over longer distances. To better understand the mechanism of parasite elimination in vivo, we monitored the dynamics of CD8+ T cells in the livers of naïve, immunized and sporozoite-infected mice by intravital microscopy. We found that immunization of BALB/c mice with attenuated P. yoelii 17XNL sporozoites significantly increases the velocity of CD8+ T cells patrolling the hepatic microvasculature from 2.69±0.34 μm/min in naïve mice to 5.74±0.66 μm/min, 9.26±0.92 μm/min, and 7.11±0.73 μm/min in mice immunized with irradiated, early genetically attenuated (Pyuis4-deficient), and late genetically attenuated (Pyfabb/f-deficient) parasites, respectively. Sporozoite infection of immunized mice revealed a 97% and 63% reduction in liver stage density and volume, respectively, compared to naïve controls. To examine cellular mechanisms of immunity in situ, naïve mice were passively immunized with hepatic or splenic CD8+ T cells. Unexpectedly, adoptive transfer rendered the motile CD8+ T cells from immunized mice immotile in the liver of P. yoelii infected mice. Similarly, when mice were simultaneously inoculated with viable sporozoites and CD8+ T cells, velocities 18 h later were also significantly reduced to 0.68±0.10 μm/min, 1.53±0.22 μm/min, and 1.06±0.26 μm/min for CD8+ T cells from mice immunized with irradiated wild type sporozoites, Pyfabb/f-deficient parasites, and P. yoelii CS280-288 peptide, respectively. Because immobilized CD8+ T cells are unable to make contact with infected hepatocytes, soluble mediators could potentially play a key role in parasite elimination under these experimental conditions.
Details
- Title: Subtitle
- In vivo CD8+ T cell dynamics in the liver of Plasmodium yoelii immunized and infected mice
- Creators
- Mynthia Cabrera - Department of Microbiology, Division of Medical Parasitology, New York University School of Medicine, New York, United States of AmericaLecia L PeweJohn T HartyUte Frevert
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(8), pp.e70842-e70842
- Publisher
- United States
- DOI
- 10.1371/journal.pone.0070842
- PMID
- 23967119
- PMCID
- PMC3743839
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- R01 AI070894 / NIAID NIH HHS R01 AI095178 / NIAID NIH HHS R01 AI100527 / NIAID NIH HHS AI85515 / NIAID NIH HHS AI95178 / NIAID NIH HHS S10 RR019288 / NCRR NIH HHS R01 AI085515 / NIAID NIH HHS AI1000527 / NIAID NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Pathology
- Record Identifier
- 9984046905902771
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