Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection

Daniel Fernandez-Ruiz, Wei Yi Ng, Lauren E. Holz, Joel Z. Ma, Ali Zaid, Yik Chun Wong, Lei Shong Lau, Vanessa Mollard, Anton Cozijnsen, Nicholas Collins, Jessica Li, Gayle M. Davey, Yu Kato, Sapna Devi, Roghieh Skandari, Michael Pauley, Jonathan H. Manton, Dale I. Godfrey, Asolina Braun, Szun Szun TayPeck Szee Tan, David G. Bowen, Friedrich Koch-Nolte, Björn Rissiek, Francis R. Carbone, Brendan S. Crabb, Mireille Lahoud, Ian A. Cockburn, Scott N. Mueller, Patrick Bertolino, Geoffrey I. McFadden, Irina Caminschi, William R. Heath

Research output: Contribution to journalArticleResearchpeer-review

114 Citations (Scopus)

Abstract

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8+ T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity.

Original languageEnglish
Pages (from-to)889-902
Number of pages14
JournalImmunity
Volume45
Issue number4
DOIs
Publication statusPublished - 18 Oct 2016

Keywords

  • CD8 T cells
  • Clec9A
  • liver
  • liver surveillance
  • malaria
  • memory T cells
  • sporozoite
  • tissue-resident memory
  • vaccine

Cite this

Fernandez-Ruiz, D., Ng, W. Y., Holz, L. E., Ma, J. Z., Zaid, A., Wong, Y. C., Lau, L. S., Mollard, V., Cozijnsen, A., Collins, N., Li, J., Davey, G. M., Kato, Y., Devi, S., Skandari, R., Pauley, M., Manton, J. H., Godfrey, D. I., Braun, A., ... Heath, W. R. (2016). Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection. Immunity, 45(4), 889-902. https://doi.org/10.1016/j.immuni.2016.08.011