Expeditious Recruitment of Circulating Memory CD8 T cells to the Liver Facilitates Control of Malaria

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Nov 3

PMID 34731605

Citations 18

Authors

Mitchell N Lefebvre

Fionna A Surette

Scott M Anthony

Rahul Vijay

Isaac J Jensen

Lecia L Pewe

Lisa S Hancox

Natalija Van Braeckel-Budimir

Stephanie van de Wall

Stina L Urban

Madison R Mix

Samarchith P Kurup

Vladimir P Badovinac

Noah S Butler

John T Harty

Affiliations

Soon will be listed here.

Abstract

Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector memory CD8 T cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections and mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires CD8 T cell-intrinsic LFA-1 expression and the presence of liver phagocytes. Rapid Tem liver infiltration is distinct from recruitment to other non-lymphoid tissues in that it occurs both in the absence of liver tissue resident memory "sensing-and-alarm" function and ∼42 hours earlier than in lung infection by influenza virus. These data demonstrate relevance for Tem in protection against malaria and provide generalizable mechanistic insights germane to control of liver infections.

Citing Articles

Early Activation of Lung CD8 T Cells After Immunization with Live Malaria Sporozoites.

van Schuijlenburg R, Naar C, van der Wees S, Chevalley-Maurel S, Duszenko N, de Bes-Roeleveld H Pathog Immun. 2025; 10(2):46-68.

PMID: 40062354 PMC: 11888604. DOI: 10.20411/pai.v10i2.794.

Memory Cells in Infection and Autoimmunity: Mechanisms, Functions, and Therapeutic Implications.

Giri S, Batra L Vaccines (Basel). 2025; 13(2).

PMID: 40006751 PMC: 11860616. DOI: 10.3390/vaccines13020205.

A replication competent Plasmodium falciparum parasite completely attenuated by dual gene deletion.

Goswami D, Patel H, Betz W, Armstrong J, Camargo N, Patil A EMBO Mol Med. 2024; 16(4):723-754.

PMID: 38514791 PMC: 11018819. DOI: 10.1038/s44321-024-00057-7.

CD8 Trms against malaria liver-stage: prospects and challenges.

Zhu C, Jiao S, Xu W Front Immunol. 2024; 15:1344941.

PMID: 38318178 PMC: 10839007. DOI: 10.3389/fimmu.2024.1344941.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

MacMillen Z, Hatzakis K, Simpson A, Shears M, Watson F, Erasmus J NPJ Vaccines. 2024; 9(1):12.

PMID: 38200025 PMC: 10781674. DOI: 10.1038/s41541-023-00799-4.

References

Kurup S, Butler N, Harty J . T cell-mediated immunity to malaria. Nat Rev Immunol. 2019; 19(7):457-471. PMC: 6599480. DOI: 10.1038/s41577-019-0158-z. View

Borges da Silva H, Wang H, Qian L, Hogquist K, Jameson S . ARTC2.2/P2RX7 Signaling during Cell Isolation Distorts Function and Quantification of Tissue-Resident CD8 T Cell and Invariant NKT Subsets. J Immunol. 2019; 202(7):2153-2163. PMC: 6424602. DOI: 10.4049/jimmunol.1801613. View

Guidotti L, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L . Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell. 2015; 161(3):486-500. PMC: 11630812. DOI: 10.1016/j.cell.2015.03.005. View

Mackay L, Minnich M, Kragten N, Liao Y, Nota B, Seillet C . Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science. 2016; 352(6284):459-63. DOI: 10.1126/science.aad2035. View

Schmidt N, Podyminogin R, Butler N, Badovinac V, Tucker B, Bahjat K . Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria. Proc Natl Acad Sci U S A. 2008; 105(37):14017-22. PMC: 2544571. DOI: 10.1073/pnas.0805452105. View

Panes J, Perry M, Anderson D, Manning A, Leone B, Cepinskas G . Regional differences in constitutive and induced ICAM-1 expression in vivo. Am J Physiol. 1995; 269(6 Pt 2):H1955-64. DOI: 10.1152/ajpheart.1995.269.6.H1955. View

Pearen M, Lim H, Gratte F, Fernandez-Rojo M, Nawaratna S, Gobert G . Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology. J Vis Exp. 2020; (157). DOI: 10.3791/60992. View

Crispe I . Migration of lymphocytes into hepatic sinusoids. J Hepatol. 2012; 57(1):218-20. DOI: 10.1016/j.jhep.2011.12.035. View

Middleton J, Patterson A, Gardner L, Schmutz C, Ashton B . Leukocyte extravasation: chemokine transport and presentation by the endothelium. Blood. 2002; 100(12):3853-60. DOI: 10.1182/blood.V100.12.3853. View

10.

Ozaki L, Gwadz R, GODSON G . Simple centrifugation method for rapid separation of sporozoites from mosquitoes. J Parasitol. 1984; 70(5):831-3. View

11.

Osborn J, Hobbs S, Mooster J, Khan T, Kilgore A, Harbour J . Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance. PLoS Pathog. 2019; 15(3):e1007633. PMC: 6420010. DOI: 10.1371/journal.ppat.1007633. View

12.

Seder R, Chang L, Enama M, Zephir K, Sarwar U, Gordon I . Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013; 341(6152):1359-65. DOI: 10.1126/science.1241800. View

13.

Agnandji S, Lell B, Fernandes J, Abossolo B, Methogo B, Lumeka Kabwende A . A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012; 367(24):2284-95. PMC: 10915853. DOI: 10.1056/NEJMoa1208394. View

14.

Doll K, Harty J . Correlates of protective immunity following whole sporozoite vaccination against malaria. Immunol Res. 2014; 59(1-3):166-76. PMC: 4382868. DOI: 10.1007/s12026-014-8525-0. View

15.

Nolz J . Molecular mechanisms of CD8(+) T cell trafficking and localization. Cell Mol Life Sci. 2015; 72(13):2461-73. PMC: 4458431. DOI: 10.1007/s00018-015-1835-0. View

16.

Doll K, Pewe L, Kurup S, Harty J . Discriminating Protective from Nonprotective Plasmodium-Specific CD8+ T Cell Responses. J Immunol. 2016; 196(10):4253-62. PMC: 4868661. DOI: 10.4049/jimmunol.1600155. View

17.

Griffith J, Sokol C, Luster A . Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014; 32:659-702. DOI: 10.1146/annurev-immunol-032713-120145. View

18.

Olson J, McDonald-Hyman C, Jameson S, Hamilton S . Effector-like CD8⁺ T cells in the memory population mediate potent protective immunity. Immunity. 2013; 38(6):1250-60. PMC: 3703254. DOI: 10.1016/j.immuni.2013.05.009. View

19.

Lee W, Kubes P . Leukocyte adhesion in the liver: distinct adhesion paradigm from other organs. J Hepatol. 2008; 48(3):504-12. DOI: 10.1016/j.jhep.2007.12.005. View

20.

Nussenzweig R, Vanderberg J, MOST H, Orton C . Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967; 216(5111):160-2. DOI: 10.1038/216160a0. View