Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

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.

• Authors: 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 Tay, Peck 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
• Journal: Immunity (Immunity) Vol. 45 Issue 4 Pg. 889-902 (10 18 2016) ISSN: 1097-4180 [Electronic] United States
• PMID: 27692609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Malaria Vaccines

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, parasitology)
• Culicidae
• Dendritic Cells (immunology, parasitology)
• Hepatocytes (immunology, parasitology)
• Immunologic Memory (immunology)
• Liver (immunology, parasitology)
• Liver Diseases (immunology, parasitology)
• Malaria (immunology)
• Malaria Vaccines (immunology)
• Mice
• Plasmodium berghei (immunology)
• Sporozoites (immunology, parasitology)
• Vaccination (methods)