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 Tay & 13 others 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

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91 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., ... 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
Fernandez-Ruiz, Daniel ; Ng, Wei Yi ; Holz, Lauren E. ; Ma, Joel Z. ; Zaid, Ali ; Wong, Yik Chun ; Lau, Lei Shong ; Mollard, Vanessa ; Cozijnsen, Anton ; Collins, Nicholas ; Li, Jessica ; Davey, Gayle M. ; Kato, Yu ; Devi, Sapna ; Skandari, Roghieh ; Pauley, Michael ; Manton, Jonathan H. ; Godfrey, Dale I. ; Braun, Asolina ; Tay, Szun Szun ; Tan, Peck Szee ; Bowen, David G. ; Koch-Nolte, Friedrich ; Rissiek, Björn ; Carbone, Francis R. ; Crabb, Brendan S. ; Lahoud, Mireille ; Cockburn, Ian A. ; Mueller, Scott N. ; Bertolino, Patrick ; McFadden, Geoffrey I. ; Caminschi, Irina ; Heath, William R. / Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection. In: Immunity. 2016 ; Vol. 45, No. 4. pp. 889-902.
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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.",
keywords = "CD8 T cells, Clec9A, liver, liver surveillance, malaria, memory T cells, sporozoite, tissue-resident memory, vaccine",
author = "Daniel Fernandez-Ruiz and Ng, {Wei Yi} and Holz, {Lauren E.} and Ma, {Joel Z.} and Ali Zaid and Wong, {Yik Chun} and Lau, {Lei Shong} and Vanessa Mollard and Anton Cozijnsen and Nicholas Collins and Jessica Li and Davey, {Gayle M.} and Yu Kato and Sapna Devi and Roghieh Skandari and Michael Pauley and Manton, {Jonathan H.} and Godfrey, {Dale I.} and Asolina Braun and Tay, {Szun Szun} and Tan, {Peck Szee} and Bowen, {David G.} and Friedrich Koch-Nolte and Bj{\"o}rn Rissiek and Carbone, {Francis R.} and Crabb, {Brendan S.} and Mireille Lahoud and Cockburn, {Ian A.} and Mueller, {Scott N.} and Patrick Bertolino and McFadden, {Geoffrey I.} and Irina Caminschi and Heath, {William R.}",
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Fernandez-Ruiz, D, Ng, WY, Holz, LE, Ma, JZ, Zaid, A, Wong, YC, Lau, LS, Mollard, V, Cozijnsen, A, Collins, N, Li, J, Davey, GM, Kato, Y, Devi, S, Skandari, R, Pauley, M, Manton, JH, Godfrey, DI, Braun, A, Tay, SS, Tan, PS, Bowen, DG, Koch-Nolte, F, Rissiek, B, Carbone, FR, Crabb, BS, Lahoud, M, Cockburn, IA, Mueller, SN, Bertolino, P, McFadden, GI, Caminschi, I & Heath, WR 2016, 'Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection', Immunity, vol. 45, no. 4, pp. 889-902. https://doi.org/10.1016/j.immuni.2016.08.011

Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection. / Fernandez-Ruiz, Daniel; Ng, Wei Yi; Holz, Lauren E.; Ma, Joel Z.; Zaid, Ali; Wong, Yik Chun; Lau, Lei Shong; Mollard, Vanessa; Cozijnsen, Anton; Collins, Nicholas; Li, Jessica; Davey, Gayle M.; Kato, Yu; Devi, Sapna; Skandari, Roghieh; Pauley, Michael; Manton, Jonathan H.; Godfrey, Dale I.; Braun, Asolina; Tay, Szun Szun; Tan, Peck Szee; Bowen, David G.; Koch-Nolte, Friedrich; Rissiek, Björn; Carbone, Francis R.; Crabb, Brendan S.; Lahoud, Mireille; Cockburn, Ian A.; Mueller, Scott N.; Bertolino, Patrick; McFadden, Geoffrey I.; Caminschi, Irina; Heath, William R.

In: Immunity, Vol. 45, No. 4, 18.10.2016, p. 889-902.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Liver-resident memory CD8+ T cells rorm a front-line defense against malaria liver-stage infection

AU - Fernandez-Ruiz, Daniel

AU - Ng, Wei Yi

AU - Holz, Lauren E.

AU - Ma, Joel Z.

AU - Zaid, Ali

AU - Wong, Yik Chun

AU - Lau, Lei Shong

AU - Mollard, Vanessa

AU - Cozijnsen, Anton

AU - Collins, Nicholas

AU - Li, Jessica

AU - Davey, Gayle M.

AU - Kato, Yu

AU - Devi, Sapna

AU - Skandari, Roghieh

AU - Pauley, Michael

AU - Manton, Jonathan H.

AU - Godfrey, Dale I.

AU - Braun, Asolina

AU - Tay, Szun Szun

AU - Tan, Peck Szee

AU - Bowen, David G.

AU - Koch-Nolte, Friedrich

AU - Rissiek, Björn

AU - Carbone, Francis R.

AU - Crabb, Brendan S.

AU - Lahoud, Mireille

AU - Cockburn, Ian A.

AU - Mueller, Scott N.

AU - Bertolino, Patrick

AU - McFadden, Geoffrey I.

AU - Caminschi, Irina

AU - Heath, William R.

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - Clec9A

KW - liver

KW - liver surveillance

KW - malaria

KW - memory T cells

KW - sporozoite

KW - tissue-resident memory

KW - vaccine

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U2 - 10.1016/j.immuni.2016.08.011

DO - 10.1016/j.immuni.2016.08.011

M3 - Article

VL - 45

SP - 889

EP - 902

JO - Immunity

JF - Immunity

SN - 1074-7613

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