MAIT Cell Activation is Associated with Disease Severity Markers in Acute Hantavirus Infection

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2021 Mar 25

PMID 33763658

Citations 14

Authors

Kimia T Maleki

Johanna Tauriainen

Marina Garcia

Priscilla F Kerkman

Wanda Christ

Joana Dias

Julia Wigren Bystrom

Edwin Leeansyah

Mattias N Forsell

Hans-Gustaf Ljunggren

Clas Ahlm

Niklas K Bjorkstrom

Johan K Sandberg

Jonas Klingstrom

Affiliations

Soon will be listed here.

Abstract

Hantaviruses are zoonotic RNA viruses that cause severe acute disease in humans. Infected individuals have strong inflammatory responses that likely cause immunopathology. Here, we studied the response of mucosal-associated invariant T (MAIT) cells in peripheral blood of individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus, a hantavirus endemic in Europe. We show that MAIT cell levels decrease in the blood during HFRS and that residual MAIT cells are highly activated. This activation correlates with HFRS severity markers. activation of MAIT cells by hantavirus-exposed antigen-presenting cells is dependent on type I interferons (IFNs) and independent of interleukin-18 (IL-18). These findings highlight the role of type I IFNs in virus-driven MAIT cell activation and suggest a potential role of MAIT cells in the disease pathogenesis of viral infections.

Citing Articles

The Role of Mucosal-Associated Invariant T Cells in Viral Infections and Their Function in Vaccine Development.

Sugimoto C, Wakao H Vaccines (Basel). 2025; 13(2).

PMID: 40006702 PMC: 11860804. DOI: 10.3390/vaccines13020155.

Inflammation and Microbial Translocation Correlate with Reduced MAIT Cells in People with HIV.

Ryu A, Clagett B, Freeman M Pathog Immun. 2024; 10(1):19-46.

PMID: 39635460 PMC: 11613984. DOI: 10.20411/pai.v10i1.746.

Replication kinetics of pathogenic Eurasian orthohantaviruses in human mesangial cells.

Boegelein L, Schreiber P, Philipp A, Nusshag C, Essbauer S, Zeier M Virol J. 2024; 21(1):241.

PMID: 39354507 PMC: 11446005. DOI: 10.1186/s12985-024-02517-5.

Reduction in mucosal-associated invariant T cells (MAIT) in APECED patients is associated with elevated serum IFN-γ concentration.

Hetemaki I, Sarkkinen J, Wong H, Heikkila N, Laakso S, Miettinen S Eur J Immunol. 2024; 54(12):e2451189.

PMID: 39292205 PMC: 11628920. DOI: 10.1002/eji.202451189.

Innate lymphoid cells are activated in HFRS, and their function can be modulated by hantavirus-induced type I interferons.

Garcia M, Carrasco Garcia A, Weigel W, Christ W, Lira-Junior R, Wirth L PLoS Pathog. 2024; 20(7):e1012390.

PMID: 39038044 PMC: 11293681. DOI: 10.1371/journal.ppat.1012390.

References

Avsic-Zupanc T, Petrovec M, Furlan P, KAPS R, Elgh F, Lundkvist A . Hemorrhagic fever with renal syndrome in the Dolenjska region of Slovenia--a 10-year survey. Clin Infect Dis. 2000; 28(4):860-5. DOI: 10.1086/515185. View

Outinen T, Laine O, Makela S, Porsti I, Huhtala H, Vaheri A . Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients. Infect Dis (Lond). 2016; 48(9):682-7. DOI: 10.1080/23744235.2016.1192719. View

Ussher J, Willberg C, Klenerman P . MAIT cells and viruses. Immunol Cell Biol. 2018; 96(6):630-641. PMC: 6055725. DOI: 10.1111/imcb.12008. View

Freeman M, Morris S, Lederman M . CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4 T Cells. Pathog Immun. 2017; 2(3):335-351. PMC: 5578469. DOI: 10.20411/pai.v2i3.136. View

Nuutinen H, Vuoristo M, Farkkila M, Kahri A, Seppala K, Valtonen V . Hemorrhagic gastropathy in epidemic nephropathy. Gastrointest Endosc. 1992; 38(4):476-80. DOI: 10.1016/s0016-5107(92)70480-5. View

Loh L, Wang Z, Sant S, Koutsakos M, Jegaskanda S, Corbett A . Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation. Proc Natl Acad Sci U S A. 2016; 113(36):10133-8. PMC: 5018778. DOI: 10.1073/pnas.1610750113. View

Fernandez C, Amarasena T, Kelleher A, Rossjohn J, McCluskey J, Godfrey D . MAIT cells are depleted early but retain functional cytokine expression in HIV infection. Immunol Cell Biol. 2014; 93(2):177-88. DOI: 10.1038/icb.2014.91. View

Jouan Y, Guillon A, Gonzalez L, Perez Y, Boisseau C, Ehrmann S . Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients. J Exp Med. 2020; 217(12). PMC: 7472174. DOI: 10.1084/jem.20200872. View

Saksida A, Wraber B, Avsic-Zupanc T . Serum levels of inflammatory and regulatory cytokines in patients with hemorrhagic fever with renal syndrome. BMC Infect Dis. 2011; 11:142. PMC: 3114737. DOI: 10.1186/1471-2334-11-142. View

10.

Ma Y, Wang J, Yuan B, Wang M, Zhang Y, Xu Z . HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. PLoS Negl Trop Dis. 2013; 7(2):e2076. PMC: 3585118. DOI: 10.1371/journal.pntd.0002076. View

11.

Hildebrand D, Bode K, Riess D, Cerny D, Waldhuber A, Rommler F . Granzyme A produces bioactive IL-1β through a nonapoptotic inflammasome-independent pathway. Cell Rep. 2014; 9(3):910-7. DOI: 10.1016/j.celrep.2014.10.003. View

12.

Krakauer T, LeDuc J, KRAKAUER H . Serum levels of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 in hemorrhagic fever with renal syndrome. Viral Immunol. 1995; 8(2):75-9. DOI: 10.1089/vim.1995.8.75. View

13.

Lamichhane R, Galvin H, Hannaway R, de la Harpe S, Munro F, Tyndall J . Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation. Eur J Immunol. 2019; 50(2):178-191. DOI: 10.1002/eji.201948279. View

14.

Provine N, Klenerman P . MAIT Cells in Health and Disease. Annu Rev Immunol. 2020; 38:203-228. DOI: 10.1146/annurev-immunol-080719-015428. View

15.

Hjertqvist M, Klein S, Ahlm C, Klingstrom J . Mortality rate patterns for hemorrhagic fever with renal syndrome caused by Puumala virus. Emerg Infect Dis. 2010; 16(10):1584-6. PMC: 3294390. DOI: 10.3201/eid1610.100242. View

16.

Linderholm M, Ahlm C, Settergren B, Waage A, Tarnvik A . Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J Infect Dis. 1996; 173(1):38-43. DOI: 10.1093/infdis/173.1.38. View

17.

Dias J, Hengst J, Parrot T, Leeansyah E, Lunemann S, Malone D . Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells. J Hepatol. 2019; 71(2):301-312. PMC: 6642010. DOI: 10.1016/j.jhep.2019.04.009. View

18.

Temonen M, Mustonen J, Helin H, Pasternack A, Vaheri A, Holthofer H . Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study. Clin Immunol Immunopathol. 1996; 78(1):47-55. DOI: 10.1006/clin.1996.0007. View

19.

Reantragoon R, Corbett A, Sakala I, Gherardin N, Furness J, Chen Z . Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med. 2013; 210(11):2305-20. PMC: 3804952. DOI: 10.1084/jem.20130958. View

20.

Tuuminen T, Kekalainen E, Makela S, Ala-Houhala I, Ennis F, Hedman K . Human CD8+ T cell memory generation in Puumala hantavirus infection occurs after the acute phase and is associated with boosting of EBV-specific CD8+ memory T cells. J Immunol. 2007; 179(3):1988-95. DOI: 10.4049/jimmunol.179.3.1988. View