Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection
Open accessAbstract
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.
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BackgroundInfluentialHuman Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence
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“…transcription factor expression, and the capacity to maintain efficient interleukin (IL)-2 and interferon (IFN)- g production in the tolerogenic liver, but the cellular processes and metabolic state driving these adaptations have not been defined (Fernandez-Ruiz et al., 2016; Tse et al., 2011).”
BackgroundImmune surveillance of the liver by T cells
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Tissue CD14+CD8+T-cells reprogrammed by myeloid cells and modulated by LPS
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“Global CD8 + T RM cells (defined by CD69 and CD103 co-expression) are flushed out during liver transplant donor organ perfusion at similar frequencies to those isolated from digested liver tissue, consistent with a predominantly intravascular localization 6,9 .”
Prime and target immunization protects against liver-stage malaria in mice
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Tissue-resident memory T cells in the skin
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Self-citationLiver sampling: a vital window into HBV pathogenesis on the path to functional cure
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mRNA vaccine against malaria tailored for liver-resident memory T cells
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Self-citationTissue-specific differentiation of CD8+ resident memory T cells
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T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development.
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Prime-and-Trap Malaria Vaccination To Generate Protective CD8+ Liver-Resident Memory T Cells
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The Roles of CCR7 for the Homing of Memory CD8+ T Cells into Their Survival Niches
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Vaccines against malaria—still a long way to go
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Self-citationTissue-resident memory CD8+ T cells in cancer immunology and immunotherapy
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Tissue-Resident Memory T Cells in Mice and Humans: Towards a Quantitative Ecology
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“Although saturation in TRM formation must be carefully distinguished from saturation of other upstream immune responses (78), identifying potential carrying capacities is important as the density of Ag-specific TRM within a tissue can influence the efficacy of protection (11, 58).”
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“Instead, peripheral T cell responses are assessed, but those responses may not represent responses in the liver [1,45,49].”
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Epigenetic Regulation of T Cell Memory: Recalling Therapeutic Implications.
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Self-citationThe liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59 · see citing works
- Authors
- 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., Tay, S. S., Tan, P. S., Bowen, D. G., Koch-Nolte, F., Rissiek, B., Carbone, F. R., Crabb, B. S., Lahoud, M., Cockburn, I. A., Mueller, S. N., Bertolino, P., McFadden, G. I., Caminschi, I., & Heath, W. R.
- Affiliations
- Burnet Institute (AU)
- The University of Melbourne (AU)
- The University of Sydney (AU)
- University Medical Center Hamburg-Eppendorf (DE)
- Australian National University (AU)
- Corresponding author
- Caminschi, Irina
- Heath, William R.
- ORCID
- Ng, Wei Yi
- Holz, Lauren E.
- Ma, Joel Z.
- Zaid, Ali
- Mollard, Vanessa
- Cozijnsen, Anton
- Li, Jessica
- Davey, Gayle M.
- Kato, Yu
- Devi, Sapna
- Pauley, Michael
- Manton, Jonathan H.
- Godfrey, Dale I.
- Braun, Asolina
- Tay, Szun Szun
- Tan, Peck Szee
- Bowen, David G.
- Rissiek, Björn
- Crabb, Brendan S.
- Lahoud, Mireille
- Cockburn, Ian A.
- Mueller, Scott N.
- Bertolino, Patrick
- McFadden, Geoffrey I.
- Caminschi, Irina
- Heath, William R.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 45
- Issue
- 4
- Pages
- 889-902
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2525642000
- Cited by
- 438
- References
- 0
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 38 · 2023: 41 · 2022: 42 · 2021: 70 · 2020: 59 · 2019: 47 · 2018: 47 · 2017: 18 · 2016: 3
- FWCI
- 38.01
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-10-15)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Griffith Research Online (submittedVersion)
- Funders
- National Health and Medical Research Council of Australia
- Australian Research Council
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- malaria, liver-stage immunity, tissue-resident memory T cells, CD8+ T cells, Plasmodium, dendritic cell priming, liver inflammation, malaria vaccine
- MeSH terms
- Animals, Dendritic Cells, Immunologic Memory, Liver, Liver Diseases, Malaria, Culicidae, Plasmodium berghei, Vaccination, Malaria Vaccines, CD8-Positive T-Lymphocytes, Hepatocytes, Sporozoites, Mice
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