MAIT Cells Are Activated in Acute Dengue Virus Infection and After in Vitro Zika Virus Infection

Overview

Journal PLoS Negl Trop Dis

Specialties Infectious Diseases
Tropical Medicine

Date 2018 Jan 23

PMID 29357366

Citations 26

Authors

Dominic Paquin-Proulx

Vivian I Avelino-Silva

Bianca A N Santos

Nathalia Silveira Barsotti

Fabiana Siroma

Jessica Fernandes Ramos

Adriana Coracini Tonacio

Alice Song

Alvino Maestri

Natalia Barros Cerqueira

Alvina Clara Felix

Jose Eduardo Levi

Benjamin C Greenspun

Miguel de Mulder Rougvie

Michael G Rosenberg

Douglas F Nixon

Esper G Kallas

Affiliations

Soon will be listed here.

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

Citing Articles

Biological functions and therapeutic applications of human mucosal-associated invariant T cells.

Fang Y, Chen Y, Niu S, Lyu Z, Tian Y, Shen X J Biomed Sci. 2025; 32(1):32.

PMID: 40025566 PMC: 11871619. DOI: 10.1186/s12929-025-01125-x.

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.

The Emerging Role of MAIT Cell Responses in Viral Infections.

Sandberg J, Leeansyah E, Eller M, Shacklett B, Paquin-Proulx D J Immunol. 2023; 211(4):511-517.

PMID: 37549397 PMC: 10421619. DOI: 10.4049/jimmunol.2300147.

-the struggles and battles of innate-like effector T lymphocytes with microbes.

Joyce S, Okoye G, Driver J Front Immunol. 2023; 14:1117825.

PMID: 37168859 PMC: 10165076. DOI: 10.3389/fimmu.2023.1117825.

Varicella Zoster Virus infects mucosal associated Invariant T cells.

Purohit S, Corbett A, Slobedman B, Abendroth A Front Immunol. 2023; 14:1121714.

PMID: 37006246 PMC: 10063790. DOI: 10.3389/fimmu.2023.1121714.

References

Dias J, Leeansyah E, Sandberg J . Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines. Proc Natl Acad Sci U S A. 2017; 114(27):E5434-E5443. PMC: 5502643. DOI: 10.1073/pnas.1705759114. View

Gold M, McLaren J, Reistetter J, Smyk-Pearson S, Ladell K, Swarbrick G . MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. J Exp Med. 2014; 211(8):1601-10. PMC: 4113934. DOI: 10.1084/jem.20140507. View

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

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

van de Weg C, Koraka P, van Gorp E, Mairuhu A, Supriatna M, Soemantri A . Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity. J Clin Virol. 2011; 53(1):38-42. DOI: 10.1016/j.jcv.2011.09.028. View

Teunissen M, Yeremenko N, Baeten D, Chielie S, Spuls P, de Rie M . The IL-17A-producing CD8+ T-cell population in psoriatic lesional skin comprises mucosa-associated invariant T cells and conventional T cells. J Invest Dermatol. 2014; 134(12):2898-2907. DOI: 10.1038/jid.2014.261. View

Pacsa A, Agarwal R, Elbishbishi E, Chaturvedi U, Nagar R, Mustafa A . Role of interleukin-12 in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol. 2000; 28(2):151-5. DOI: 10.1111/j.1574-695X.2000.tb01470.x. View

Messina J, Kraemer M, Brady O, Pigott D, Shearer F, Weiss D . Mapping global environmental suitability for Zika virus. Elife. 2016; 5. PMC: 4889326. DOI: 10.7554/eLife.15272. View

Leeansyah E, Svard J, Dias J, Buggert M, Nystrom J, Quigley M . Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection. PLoS Pathog. 2015; 11(8):e1005072. PMC: 4546682. DOI: 10.1371/journal.ppat.1005072. View

10.

Joao E, Fragoso da Silveira Gouvea M, Benamor Teixeira M, Mendes-Silva W, Silva Esteves J, Santos E . Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected Pregnant Woman. Pediatr Infect Dis J. 2017; 36(5):500-501. DOI: 10.1097/INF.0000000000001482. View

11.

Kjer-Nielsen L, Patel O, Corbett A, Le Nours J, Meehan B, Liu L . MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012; 491(7426):717-23. DOI: 10.1038/nature11605. View

12.

Paquin-Proulx D, Greenspun B, Costa E, Segurado A, Kallas E, Nixon D . MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications. PLoS One. 2017; 12(4):e0175345. PMC: 5383303. DOI: 10.1371/journal.pone.0175345. View

13.

Pang J, Thein T, Lye D, Leo Y . Differential clinical outcome of dengue infection among patients with and without HIV infection: a matched case-control study. Am J Trop Med Hyg. 2015; 92(6):1156-1162. PMC: 4458819. DOI: 10.4269/ajtmh.15-0031. View

14.

Rothman A . Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol. 2011; 11(8):532-43. DOI: 10.1038/nri3014. View

15.

Salou M, Franciszkiewicz K, Lantz O . MAIT cells in infectious diseases. Curr Opin Immunol. 2017; 48:7-14. DOI: 10.1016/j.coi.2017.07.009. View

16.

de Matos A, Carvalho K, Santoro Rosa D, Villas-Boas L, da Silva W, Rodrigues C . CD8+ T lymphocyte expansion, proliferation and activation in dengue fever. PLoS Negl Trop Dis. 2015; 9(2):e0003520. PMC: 4326415. DOI: 10.1371/journal.pntd.0003520. View

17.

Li J, Reantragoon R, Kostenko L, Corbett A, Varigos G, Carbone F . The frequency of mucosal-associated invariant T cells is selectively increased in dermatitis herpetiformis. Australas J Dermatol. 2016; 58(3):200-204. DOI: 10.1111/ajd.12456. View

18.

Hengst J, Strunz B, Deterding K, Ljunggren H, Leeansyah E, Manns M . Nonreversible MAIT cell-dysfunction in chronic hepatitis C virus infection despite successful interferon-free therapy. Eur J Immunol. 2016; 46(9):2204-10. DOI: 10.1002/eji.201646447. View

19.

van Wilgenburg B, Scherwitzl I, Hutchinson E, Leng T, Kurioka A, Kulicke C . MAIT cells are activated during human viral infections. Nat Commun. 2016; 7:11653. PMC: 4931007. DOI: 10.1038/ncomms11653. View

20.

Tang X, Jo J, Tan A, Sandalova E, Chia A, Tan K . IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells. J Immunol. 2013; 190(7):3142-52. DOI: 10.4049/jimmunol.1203218. View