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 language | English |
|---|---|
| Pages (from-to) | 889-902 |
| Number of pages | 14 |
| Journal | Immunity |
| Volume | 45 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 18 Oct 2016 |
Keywords
- CD8 T cells
- Clec9A
- liver
- liver surveillance
- malaria
- memory T cells
- sporozoite
- tissue-resident memory
- vaccine
Cite this
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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 journal › Article › Research › peer-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
UR - http://www.scopus.com/inward/record.url?scp=84994876821&partnerID=8YFLogxK
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
IS - 4
ER -