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01-11-2018 | Original Investigation

The interplay between local immune response and Epstein–Barr virus-infected tonsillar cells could lead to viral infection control

Authors: Aldana G. Vistarop, Melina Cohen, Fuad Huaman, Lucia Irazu, Marcelo Rodriguez, Elena De Matteo, María Victoria Preciado, Paola A. Chabay

Published in: Medical Microbiology and Immunology | Issue 5-6/2018

Abstract

Epstein Barr virus (EBV) gains access to the host through tonsillar crypts. Our aim was to characterize microenvironment composition around EBV+ cells in tonsils from pediatric carriers, to disclose its role on viral pathogenesis. LMP1 expression, assessed by immunohistochemistry (IHC), was used to discriminate EBV + and – zones in 41 tonsil biopsies. Three regions were defined: Subepithelial (SE), interfollicular (IF) and germinal center (GC). CD8, GrB, CD68, IL10, Foxp3, PD1, CD56 and CD4 markers were evaluated by IHC; positive cells/100 total cells were counted. CD8+, GrB+, CD68+ and IL10+ cells were prevalent in EBV+ zones at the SE region (p < 0.0001, p = 0.03, p = 0.002 and p = 0.002 respectively, Wilcoxon test). CD4+ and CD68+ cell count were higher in EBV + GC (p = 0.01 and p = 0.0002 respectively, Wilcoxon test). Increment of CD8, GrB and CD68 at the SE region could indicate a specific response that may be due to local homing at viral entry, which could be counterbalanced by IL10, an immunosuppressive cytokine. Additionally, it could be hypothesized that CD4 augment at the GC may be involved in the EBV-induced B-cell growth control at this region, in which macrophages could also participate.

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Ok CY, Li L, Young KH (2015) EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management. Exp Mol Med 47:e132. https://doi.org/10.1038/emm.2014.82 CrossRefPubMedPubMedCentral

Young LS, Yap LF, Murray PG (2016) Epstein–Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer 16(12):789–802. https://doi.org/10.1038/nrc.2016.92 CrossRefPubMed

Münz C (2016) Epstein Barr virus—a tumor virus that needs cytotoxic lymphocytes to persist asymptomatically. Curr Opin Virol 20:34–39. https://doi.org/10.1016/j.coviro.2016.08.010 CrossRefPubMed

Rickinson AB, Long HM, Palendira U, Munz C, Hislop AD (2014) Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory. Trends Immunol 35(4):159–169. https://doi.org/10.1016/j.it.2014.01.003 CrossRefPubMed

Mesri EA, Feitelson MA, Munger K (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15(3):266–282. https://doi.org/10.1016/j.chom.2014.02.011 CrossRefPubMedPubMedCentral

Hislop AD, Taylor GS (2015) T-cell responses to EBV. Curr Top Microbiol Immunol 391:325–353. https://doi.org/10.1007/978-3-319-22834-1_11 CrossRefPubMed

Odumade OA, Hogquist KA, Balfour HH Jr (2011) Progress and problems in understanding and managing primary Epstein–Barr virus infections. Clin Microbiol Rev 24(1):193–209. https://doi.org/10.1128/CMR.00044-10 CrossRefPubMedPubMedCentral

Chabay PA, Preciado MV (2013) EBV primary infection in childhood and its relation to B-cell lymphoma development: a mini-review from a developing region. Int J Cancer 133(6):1286–1292. https://doi.org/10.1002/ijc.27858 CrossRefPubMed

Jayasooriya S, de Silva TI, Njie-Jobe J, Sanyang C, Leese AM, Bell AI, McAulay KA, Yanchun P, Long HM, Dong T, Whittle HC, Rickinson AB, Rowland-Jones SL, Hislop AD, Flanagan KL (2015) Early virological and immunological events in asymptomatic Epstein–Barr virus infection in african children. PLoS Pathog 11(3):e1004746. https://doi.org/10.1371/journal.ppat.1004746 CrossRefPubMedPubMedCentral

10.

Chijioke O, Muller A, Feederle R, Barros MH, Krieg C, Emmel V, Marcenaro E, Leung CS, Antsiferova O, Landtwing V, Bossart W, Moretta A, Hassan R, Boyman O, Niedobitek G, Delecluse HJ, Capaul R, Munz C (2013) Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein–Barr virus infection. Cell Rep 5(6):1489–1498. https://doi.org/10.1016/j.celrep.2013.11.041 CrossRefPubMedPubMedCentral

11.

Azzi T, Lunemann A, Murer A, Ueda S, Beziat V, Malmberg KJ, Staubli G, Gysin C, Berger C, Munz C, Chijioke O, Nadal D (2014) Role for early-differentiated natural killer cells in infectious mononucleosis. Blood 124(16):2533–2543. https://doi.org/10.1182/blood-2014-01-553024 CrossRefPubMedPubMedCentral

12.

Dolcetti R (2015) Cross-talk between Epstein–Barr virus and microenvironment in the pathogenesis of lymphomas. Semin Cancer Biol 34:58–69. https://doi.org/10.1016/j.semcancer.2015.04.006 CrossRefPubMed

13.

Wu R, Sattarzadeh A, Rutgers B, Diepstra A, van den Berg A, Visser L (2016) The microenvironment of classical Hodgkin lymphoma: heterogeneity by Epstein–Barr virus presence and location within the tumor. Blood Cancer J 6:e417. https://doi.org/10.1038/bcj.2016.26 CrossRefPubMedPubMedCentral

14.

Chetaille B, Bertucci F, Finetti P, Esterni B, Stamatoullas A, Picquenot JM, Copin MC, Morschhauser F, Casasnovas O, Petrella T, Molina T, Vekhoff A, Feugier P, Bouabdallah R, Birnbaum D, Olive D, Xerri L (2009) Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome. Blood 113(12):2765–3775. https://doi.org/10.1182/blood-2008-07-168096 CrossRefPubMed

15.

Barros MH, Vera-Lozada G, Soares FA, Niedobitek G, Hassan R (2012) Tumor microenvironment composition in pediatric classical Hodgkin lymphoma is modulated by age and Epstein–Barr virus infection. Int J Cancer 131(5):1142–1152. https://doi.org/10.1002/ijc.27314 CrossRefPubMed

16.

Barros MH, Hassan R, Niedobitek G (2012) Tumor-associated macrophages in pediatric classical Hodgkin lymphoma: association with Epstein–Barr virus, lymphocyte subsets, and prognostic impact. Clin Cancer Res 18(14):3762–3771. https://doi.org/10.1158/1078-0432.CCR-12-0129 CrossRefPubMed

17.

Barros MH, Segges P, Vera-Lozada G, Hassan R, Niedobitek G (2015) Macrophage polarization reflects T cell composition of tumor microenvironment in pediatric classical Hodgkin lymphoma and has impact on survival. PloS One 10(5):e0124531. https://doi.org/10.1371/journal.pone.0124531 CrossRefPubMedPubMedCentral

18.

Strowig T, Brilot F, Arrey F, Bougras G, Thomas D, Muller WA, Munz C (2008) Tonsilar NK cells restrict B cell transformation by the Epstein–Barr virus via IFN-gamma. PLoS Pathog 4(2):e27. https://doi.org/10.1371/journal.ppat.0040027 CrossRefPubMedPubMedCentral

19.

Vistarop AG, Cohen M, De Matteo E, Preciado MV, Chabay PA (2016) Analysis of Epstein–Barr virus infection models in a series of pediatric carriers from a developing country. Sci Rep 6:23303. https://doi.org/10.1038/srep23303 CrossRefPubMedPubMedCentral

20.

Fossum CC, Chintakuntlawar AV, Price DL, Garcia JJ (2016) Characterization of the oropharynx: anatomy, histology, immunology, squamous cell carcinoma and surgical resection. Histopathology. https://doi.org/10.1111/his.13140 CrossRef

21.

Balfour JHH, Verghese P (2013) Primary Epstein–Barr virus infection: impact of age at acquisition, coinfection, and viral load. J Infect Dis 207(12):1787–1789. https://doi.org/10.1093/infdis/jit096 CrossRefPubMedPubMedCentral

22.

Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le TTT, Morrison LE, Khanna R, Moss DJ, Suhrbier A, Misko IS (2001) Asymptomatic primary Epstein–Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood 98(13):3739CrossRef

23.

Scott DW, Gascoyne RD (2014) The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 14(8):517–534. https://doi.org/10.1038/nrc3774 CrossRefPubMed

24.

Dolcetti R, Dal Col J, Martorelli D, Carbone A, Klein E (2013) Interplay among viral antigens, cellular pathways and tumor microenvironment in the pathogenesis of EBV-driven lymphomas. Semin Cancer Biol 23(6, Part A):441–456. https://doi.org/10.1016/j.semcancer.2013.07.005 CrossRefPubMed

25.

Hislop AD, Kuo M, Drake-Lee AB, Akbar AN, Bergler W, Hammerschmitt N, Khan N, Palendira U, Leese AM, Timms JM, Bell AI, Buckley CD, Rickinson AB (2005) Tonsillar homing of Epstein–Barr virus-specific CD8+ T cells and the virus–host balance. J Clin Investig 115(9):2546–2555. https://doi.org/10.1172/JCI24810 CrossRefPubMed

26.

Cohen M, Vistarop AG, Huaman F, Narbaitz M, Metrebian F, De Matteo E, Preciado MV, Chabay PA (2017) Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: clinical features and survival impact. Sci Rep 7(1):10813. https://doi.org/10.1038/s41598-017-11052-z CrossRefPubMedPubMedCentral

27.

Gaudreault E, Fiola S, Olivier M, Gosselin J (2007) Epstein–Barr virus induces MCP-1 secretion by human monocytes via TLR2. J Virol 81(15):8016–8024. https://doi.org/10.1128/JVI.00403-07 CrossRefPubMedPubMedCentral

28.

Fiola S, Gosselin D, Takada K, Gosselin J (2010) TLR9 contributes to the recognition of EBV by primary monocytes and plasmacytoid dendritic cells. J Immunol 185(6):3620CrossRef

29.

Morales O, Mrizak D, Francois V, Mustapha R, Miroux C, Depil S, Decouvelaere AV, Lionne-Huyghe P, Auriault C, de Launoit Y, Pancre V, Delhem N (2014) Epstein–Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients. Br J Haematol 166(6):875–890. https://doi.org/10.1111/bjh.12980 CrossRefPubMed

30.

Basso K, Dalla-Favera R (2015) Germinal centres and B cell lymphomagenesis. Nat Rev Immunol 15(3):172–184. https://doi.org/10.1038/nri3814 CrossRefPubMed

31.

Vockerodt M, Yap L-F, Shannon-Lowe C, Curley H, Wei W, Vrzalikova K, Murray PG (2015) The Epstein–Barr virus and the pathogenesis of lymphoma. J Pathol 235(2):312–322. https://doi.org/10.1002/path.4459 CrossRefPubMed

32.

Hislop AD, Taylor GS, Sauce D, Rickinson AB (2007) Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annu Rev Immunol 25:587–617. https://doi.org/10.1146/annurev.immunol.25.022106.141553 CrossRefPubMed

33.

Savoldo B, Cubbage ML, Durett AG, Goss J, Huls MH, Liu Z, Teresita L, Gee AP, Ling PD, Brenner MK, Heslop HE, Rooney CM (2002) Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. J Immunol 168(2):909–918CrossRef

34.

Rahman ZS (2011) Impaired clearance of apoptotic cells in germinal centers: implications for loss of B cell tolerance and induction of autoimmunity. Immunol Res 51(2–3):125–133. https://doi.org/10.1007/s12026-011-8248-4 CrossRefPubMed

35.

De Silva NS, Klein U (2015) Dynamics of B cells in germinal centres. Nat Rev Immunol 15(3):137–148. https://doi.org/10.1038/nri3804 CrossRefPubMedPubMedCentral

36.

Zhang Y, Kim HJ, Yamamoto S, Kang X, Ma X (2010) Regulation of interleukin-10 gene expression in macrophages engulfing apoptotic cells. J Interferon Cytokine Res 30(3):113–122. https://doi.org/10.1089/jir.2010.0004 CrossRefPubMedPubMedCentral

Title: The interplay between local immune response and Epstein–Barr virus-infected tonsillar cells could lead to viral infection control
Authors: Aldana G. Vistarop
Melina Cohen
Fuad Huaman
Lucia Irazu
Marcelo Rodriguez
Elena De Matteo
María Victoria Preciado
Paola A. Chabay
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Medical Microbiology and Immunology / Issue 5-6/2018
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-018-0553-2

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