Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 12/2017

25.08.2017 | Original Article

Regulatory T cells and IL-10 as modulators of chikungunya disease outcome: a preliminary study

verfasst von: S. P. Kulkarni, M. Ganu, P. Jayawant, S. Thanapati, A. Ganu, A. S. Tripathy

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 12/2017

Einloggen, um Zugang zu erhalten

Abstract

Regulatory T (Treg) cells hold centre stage in regulating the immune responses in most viral infections. However, their involvement in chikungunya infection is unexplored. In the current study, the frequencies and functionality of peripheral Treg and T effector (Teff) cells were assessed during different phases of chikungunya by flow cytometry and in-vitro cytokine assays. Treg cells were also studied in rheumatoid arthritis (RA) patients, whose symptoms closely mimic chronic chikungunya arthritis patients. Frequency of Treg cells was lower in acute and chronic chikungunya arthritis patients than in recovered individuals and controls, and comparable among recovered individuals and controls. Treg/Teff ratio was lower in acute than in chronic chikungunya arthritis patients, recovered individuals and controls. Higher secretion of CHIKV specific IL-10 was observed in recovered individuals than in acute, chronic chikungunya arthritis patients and controls. Frequencies of Treg and Teff cells were higher and Treg/Teff ratio was lower in RA patients than in chronic chikungunya arthritis patients. The results indicate that reduction of Treg cells was associated with ongoing CHIKV infection and normalization of Treg cells with resolution of disease. Contrasting phenotypic data in RA and chronic chikungunya arthritis suggest an altogether different mechanism of Treg-mediated pathology in both arthritis conditions. Overall, our preliminary study, suggesting an association of peripheral Treg cells and IL-10 with recovery from chikungunya, may provide insight into chikungunya disease prognosis and warrants further study.
Literatur
1.
Zurück zum Zitat Powers AM (2015) Risks to the Americas associated with the continued expansion of chikungunya virus. J Gen Virol 96:1–5CrossRefPubMed Powers AM (2015) Risks to the Americas associated with the continued expansion of chikungunya virus. J Gen Virol 96:1–5CrossRefPubMed
2.
Zurück zum Zitat Thiberville SD, Moyen N, Dupuis-Maguiraga L, Nougairede A, Gould EA, Roques P, de Lamballerie X (2013) Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy. Antivir Res 99:345–370CrossRefPubMed Thiberville SD, Moyen N, Dupuis-Maguiraga L, Nougairede A, Gould EA, Roques P, de Lamballerie X (2013) Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy. Antivir Res 99:345–370CrossRefPubMed
4.
Zurück zum Zitat Hoarau JJ, Jaffar Bandjee MC, Krejbich Trotot P, Das T, Li-Pat-Yuen G, Dassa B et al (2010) Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol 184:5914–5927CrossRefPubMed Hoarau JJ, Jaffar Bandjee MC, Krejbich Trotot P, Das T, Li-Pat-Yuen G, Dassa B et al (2010) Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol 184:5914–5927CrossRefPubMed
5.
Zurück zum Zitat Teo TH, Lum FM, Claser C, Lulla V, Lulla A, Merits A, Renia L, Ng LF (2013) A pathogenic role for CD4+ T cells during Chikungunya virus infection in mice. J Immunol 190:259–269CrossRefPubMed Teo TH, Lum FM, Claser C, Lulla V, Lulla A, Merits A, Renia L, Ng LF (2013) A pathogenic role for CD4+ T cells during Chikungunya virus infection in mice. J Immunol 190:259–269CrossRefPubMed
6.
Zurück zum Zitat Hawman DW, Stoermer KA, Montgomery SA, Pal P, Oko L, Diamond MS, Morrison TE (2013) Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response. J Virol 87:13878–13888CrossRefPubMedPubMedCentral Hawman DW, Stoermer KA, Montgomery SA, Pal P, Oko L, Diamond MS, Morrison TE (2013) Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response. J Virol 87:13878–13888CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Hoarau JJ, Gay F, Pelle O, Samri A, Jaffar-Bandjee MC, Gasque P, Autran B (2013) Identical strength of the T cell responses against E2, nsP1 and capsid CHIKV proteins in recovered and chronic patients after the epidemics of 2005–2006 in La Reunion Island. PLoS One 8:e84695CrossRefPubMedPubMedCentral Hoarau JJ, Gay F, Pelle O, Samri A, Jaffar-Bandjee MC, Gasque P, Autran B (2013) Identical strength of the T cell responses against E2, nsP1 and capsid CHIKV proteins in recovered and chronic patients after the epidemics of 2005–2006 in La Reunion Island. PLoS One 8:e84695CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Wauquier N, Becquart P, Nkoghe D, Padilla C, Ndjoyi-Mbiguino A, Leroy EM (2011) The acute phase of Chikungunya virus infection in humans is associated with strong innate immunity and T CD8 cell activation. J Infect Dis 204:115–123CrossRefPubMed Wauquier N, Becquart P, Nkoghe D, Padilla C, Ndjoyi-Mbiguino A, Leroy EM (2011) The acute phase of Chikungunya virus infection in humans is associated with strong innate immunity and T CD8 cell activation. J Infect Dis 204:115–123CrossRefPubMed
9.
Zurück zum Zitat Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061CrossRefPubMed Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061CrossRefPubMed
10.
Zurück zum Zitat Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711CrossRefPubMedPubMedCentral Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Miyara M, Sakaguchi S (2007) Natural regulatory T cells: mechanisms of suppression. Trends Mol Med 13:108–116CrossRefPubMed Miyara M, Sakaguchi S (2007) Natural regulatory T cells: mechanisms of suppression. Trends Mol Med 13:108–116CrossRefPubMed
12.
Zurück zum Zitat Tillu H, Tripathy AS, Reshmi PV, Cecilia D (2015) Altered profile of regulatory T cells and associated cytokines in mild and moderate dengue. Eur J Clin Microbiol Infect Dis 35:453–461CrossRef Tillu H, Tripathy AS, Reshmi PV, Cecilia D (2015) Altered profile of regulatory T cells and associated cytokines in mild and moderate dengue. Eur J Clin Microbiol Infect Dis 35:453–461CrossRef
13.
Zurück zum Zitat Rathod SB, Tripathy AS (2016) TGF-beta1 and contact mediated suppression by CD4+CD25+CD127- T regulatory cells of patients with self-limiting hepatitis E. Hum Immunol 77:1254–1263CrossRefPubMed Rathod SB, Tripathy AS (2016) TGF-beta1 and contact mediated suppression by CD4+CD25+CD127- T regulatory cells of patients with self-limiting hepatitis E. Hum Immunol 77:1254–1263CrossRefPubMed
16.
Zurück zum Zitat Aletaha D, Neogi T, Silman AJ, Funovits J et al (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581CrossRefPubMed Aletaha D, Neogi T, Silman AJ, Funovits J et al (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581CrossRefPubMed
17.
Zurück zum Zitat Patil DR, Hundekar SL, Arankalle VA (2012) Expression profile of immune response genes during acute myopathy induced by chikungunya virus in a mouse model. Microbes Infect 14:457–469CrossRefPubMed Patil DR, Hundekar SL, Arankalle VA (2012) Expression profile of immune response genes during acute myopathy induced by chikungunya virus in a mouse model. Microbes Infect 14:457–469CrossRefPubMed
18.
Zurück zum Zitat Gadkari DA, Shaikh BH (1984) IgM antibody capture ELISA in the diagnosis of Japanese encephalitis, West Nile & dengue virus infections. Indian J Med Res 80:613–619PubMed Gadkari DA, Shaikh BH (1984) IgM antibody capture ELISA in the diagnosis of Japanese encephalitis, West Nile & dengue virus infections. Indian J Med Res 80:613–619PubMed
19.
Zurück zum Zitat Kumar M, Sudeep AB, Arankalle VA (2012) Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines against chikungunya virus. Vaccine 30:6142–6149CrossRefPubMed Kumar M, Sudeep AB, Arankalle VA (2012) Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines against chikungunya virus. Vaccine 30:6142–6149CrossRefPubMed
20.
Zurück zum Zitat Thanapati S, Das R, Tripathy AS (2015) Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection. Front Microbiol 6:895CrossRefPubMedPubMedCentral Thanapati S, Das R, Tripathy AS (2015) Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection. Front Microbiol 6:895CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Rathod SB, Das R, Thanapati S, Arankalle VA, Tripathy AS (2014) Suppressive activity and altered conventional phenotype markers/mediators of regulatory T cells in patients with self-limiting hepatitis E. J Viral Hepat 21:141–151CrossRefPubMed Rathod SB, Das R, Thanapati S, Arankalle VA, Tripathy AS (2014) Suppressive activity and altered conventional phenotype markers/mediators of regulatory T cells in patients with self-limiting hepatitis E. J Viral Hepat 21:141–151CrossRefPubMed
22.
Zurück zum Zitat Rathod SB, Tripathy AS (2014) Hepatitis E rORF2p stimulated and unstimulated peripheral expression profiling in patients with self-limiting hepatitis E infection. J Immunol Res 2014:565284CrossRefPubMedPubMedCentral Rathod SB, Tripathy AS (2014) Hepatitis E rORF2p stimulated and unstimulated peripheral expression profiling in patients with self-limiting hepatitis E infection. J Immunol Res 2014:565284CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Komatsu N, Takayanagi H (2015) Regulatory T cells in arthritis. Prog Mol Biol Transl Sci 136:207–215CrossRefPubMed Komatsu N, Takayanagi H (2015) Regulatory T cells in arthritis. Prog Mol Biol Transl Sci 136:207–215CrossRefPubMed
24.
Zurück zum Zitat Hunt L, Hensor EM, Nam J, Burska AN, Parmar R, Emery P, Ponchel F (2015) T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals. Ann Rheum Dis 75:1884–1889CrossRefPubMedPubMedCentral Hunt L, Hensor EM, Nam J, Burska AN, Parmar R, Emery P, Ponchel F (2015) T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals. Ann Rheum Dis 75:1884–1889CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Ng LF, Chow A, Sun YJ, Kwek DJ, Lim PL, Dimatatac F, Ng LC, Ooi EE, Choo KH, Her Z, Kourilsky P, Leo YS (2009) IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity. PLoS One 4:e4261CrossRefPubMedPubMedCentral Ng LF, Chow A, Sun YJ, Kwek DJ, Lim PL, Dimatatac F, Ng LC, Ooi EE, Choo KH, Her Z, Kourilsky P, Leo YS (2009) IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity. PLoS One 4:e4261CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Kelvin AA, Banner D, Silvi G, Moro ML, Spataro N, Gaibani P, Cavrini F, Pierro A, Rossini G, Cameron MJ, Bermejo-Martin JF, Paquette SG, Xu L, Danesh A, Farooqui A, Borghetto I, Kelvin DJ, Sambri V, Rubino S (2011) Inflammatory cytokine expression is associated with chikungunya virus resolution and symptom severity. PLoS Negl Trop Dis 5:e1279CrossRefPubMedPubMedCentral Kelvin AA, Banner D, Silvi G, Moro ML, Spataro N, Gaibani P, Cavrini F, Pierro A, Rossini G, Cameron MJ, Bermejo-Martin JF, Paquette SG, Xu L, Danesh A, Farooqui A, Borghetto I, Kelvin DJ, Sambri V, Rubino S (2011) Inflammatory cytokine expression is associated with chikungunya virus resolution and symptom severity. PLoS Negl Trop Dis 5:e1279CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Venugopalan A, Ghorpade RP, Chopra A (2013) Cytokines in acute chikungunya. PLoS One 9:e111305CrossRef Venugopalan A, Ghorpade RP, Chopra A (2013) Cytokines in acute chikungunya. PLoS One 9:e111305CrossRef
28.
Zurück zum Zitat Uhrlaub JL, Pulko V, DeFilippis VR, Broeckel R, Streblow DN, Coleman GD, Park BS, Lindo JF, Vickers I, Anzinger JJ, Nikolich-Zugich J (2014) Dysregulated TGF-beta production underlies the age-related vulnerability to Chikungunya virus. PLoS Pathog 12:e1005891CrossRef Uhrlaub JL, Pulko V, DeFilippis VR, Broeckel R, Streblow DN, Coleman GD, Park BS, Lindo JF, Vickers I, Anzinger JJ, Nikolich-Zugich J (2014) Dysregulated TGF-beta production underlies the age-related vulnerability to Chikungunya virus. PLoS Pathog 12:e1005891CrossRef
29.
Zurück zum Zitat Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, Kwek DJ, Barkham T, Yang H, Renia L, Leo YS, Ng LF (2011) Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor. J Infect Dis 203:149–157CrossRefPubMedPubMedCentral Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, Kwek DJ, Barkham T, Yang H, Renia L, Leo YS, Ng LF (2011) Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor. J Infect Dis 203:149–157CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Borgherini G, Poubeau P, Staikowsky F, Lory M, Le Moullec N, Becquart JP, Wengling C, Michault A, Paganin F (2007) Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clin Infect Dis 44:1401–1407CrossRefPubMed Borgherini G, Poubeau P, Staikowsky F, Lory M, Le Moullec N, Becquart JP, Wengling C, Michault A, Paganin F (2007) Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clin Infect Dis 44:1401–1407CrossRefPubMed
31.
Zurück zum Zitat Luhn K, Simmons CP, Moran E, Dung NT, Chau TN, Quyen NT, Thao le TT, Van Ngoc T, Dung NM, Wills B, Farrar J, McMichael AJ, Dong T, Rowland-Jones S (2007) Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection. J Exp Med 204:979–985CrossRefPubMedPubMedCentral Luhn K, Simmons CP, Moran E, Dung NT, Chau TN, Quyen NT, Thao le TT, Van Ngoc T, Dung NM, Wills B, Farrar J, McMichael AJ, Dong T, Rowland-Jones S (2007) Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection. J Exp Med 204:979–985CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Miner JJ, Aw Yeang HX, Fox JM, Taffner S, Malkova ON, Oh ST, Kim AH, Diamond MS, Lenschow DJ, Yokoyama WM (2015) Chikungunya viral arthritis in the United States: a mimic of seronegative rheumatoid arthritis. Arthritis Rheumatol 67:1214–1220CrossRefPubMedPubMedCentral Miner JJ, Aw Yeang HX, Fox JM, Taffner S, Malkova ON, Oh ST, Kim AH, Diamond MS, Lenschow DJ, Yokoyama WM (2015) Chikungunya viral arthritis in the United States: a mimic of seronegative rheumatoid arthritis. Arthritis Rheumatol 67:1214–1220CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Monte K, Wilson C, Shih FF (2008) Increased number and function of FoxP3 regulatory T cells during experimental arthritis. Arthritis Rheum 58:3730–3741CrossRefPubMedPubMedCentral Monte K, Wilson C, Shih FF (2008) Increased number and function of FoxP3 regulatory T cells during experimental arthritis. Arthritis Rheum 58:3730–3741CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS (2004) CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 50:2775–2785CrossRefPubMed van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS (2004) CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 50:2775–2785CrossRefPubMed
Metadaten
Titel
Regulatory T cells and IL-10 as modulators of chikungunya disease outcome: a preliminary study
verfasst von
S. P. Kulkarni
M. Ganu
P. Jayawant
S. Thanapati
A. Ganu
A. S. Tripathy
Publikationsdatum
25.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 12/2017
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-017-3087-4

Weitere Artikel der Ausgabe 12/2017

European Journal of Clinical Microbiology & Infectious Diseases 12/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.