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IFNγ and IL-12 Restrict Th2 Responses during Helminth/ Co-Infection and Promote IFNγ from Th2 Cells
Approximately a third of the world’s population is burdened with chronic intestinal parasitic helminth infections, causing significant morbidities. Identifying the factors that contribute to the chronicity of infection is therefore essential. Co-infection with other pathogens, which is extremely common in helminth endemic areas, may contribute to the chronicity of helminth infections. In this study, we used a mouse model to test whether the immune responses to an intestinal helminth were impaired following malaria co-infection. These two pathogens induce very different immune responses, which, until recently, were thought to be opposing and non-interchangeable. This study identified that the immune cells required for anti-helminth responses are capable of changing their phenotype and providing protection against malaria. By identifying and blocking the factors that drive this change in phenotype, we can preserve anti-helminth immune responses during co-infection. Our studies provide fresh insight into how immune responses are altered during helminth and malaria co-infection.
Vyšlo v časopise: IFNγ and IL-12 Restrict Th2 Responses during Helminth/ Co-Infection and Promote IFNγ from Th2 Cells. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004994
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004994Souhrn
Approximately a third of the world’s population is burdened with chronic intestinal parasitic helminth infections, causing significant morbidities. Identifying the factors that contribute to the chronicity of infection is therefore essential. Co-infection with other pathogens, which is extremely common in helminth endemic areas, may contribute to the chronicity of helminth infections. In this study, we used a mouse model to test whether the immune responses to an intestinal helminth were impaired following malaria co-infection. These two pathogens induce very different immune responses, which, until recently, were thought to be opposing and non-interchangeable. This study identified that the immune cells required for anti-helminth responses are capable of changing their phenotype and providing protection against malaria. By identifying and blocking the factors that drive this change in phenotype, we can preserve anti-helminth immune responses during co-infection. Our studies provide fresh insight into how immune responses are altered during helminth and malaria co-infection.
Zdroje
1. Hay SI, Okiro EA, Gething PW, Patil AP, Tatem AJ, et al. (2010) Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med 7: e1000290. doi: 10.1371/journal.pmed.1000290 20563310
2. Pullan RL, Smith JL, Jasrasaria R, Brooker SJ (2014) Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasit Vectors 7 : 37. doi: 10.1186/1756-3305-7-37 24447578
3. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, et al. (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118 : 1311–1321. doi: 10.1172/JCI34261 18382743
4. Degarege A, Animut A, Legesse M, Medhin G, Erko B (2014) Malaria and helminth co-infection and nutritional status of febrile patients in Southern Ethiopia. J Infect Public Health 7 : 32–37. doi: 10.1016/j.jiph.2013.05.007 23999346
5. Yapi RB, Hurlimann E, Houngbedji CA, Ndri PB, Silue KD, et al. (2014) Infection and Co-infection with Helminths and Plasmodium among School Children in Cote d'Ivoire: Results from a National Cross-Sectional Survey. PLoS Negl Trop Dis 8: e2913. doi: 10.1371/journal.pntd.0002913 24901333
6. Mulu A, Legesse M, Erko B, Belyhun Y, Nugussie D, et al. (2013) Epidemiological and clinical correlates of malaria-helminth co-infections in Southern Ethiopia. Malar J 12 : 227. doi: 10.1186/1475-2875-12-227 23822192
7. Kirwan P, Jackson AL, Asaolu SO, Molloy SF, Abiona TC, et al. (2010) Impact of repeated four-monthly anthelmintic treatment on Plasmodium infection in preschool children: a double-blind placebo-controlled randomized trial. BMC Infect Dis 10 : 277. doi: 10.1186/1471-2334-10-277 20858280
8. Degarege A, Animut A, Legesse M, Erko B (2010) Malaria and helminth co-infections in outpatients of Alaba Kulito Health Center, southern Ethiopia: a cross sectional study. BMC Res Notes 3 : 143. doi: 10.1186/1756-0500-3-143 20500831
9. Nacher M, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Vannaphan S, et al. (2001) Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand. Am J Trop Med Hyg 65 : 834–836. 11791982
10. Nacher M, Gay F, Singhasivanon P, Krudsood S, Treeprasertsuk S, et al. (2000) Ascaris lumbricoides infection is associated with protection from cerebral malaria. Parasite Immunol 22 : 107–113. 10672191
11. Hartgers FC, Obeng BB, Boakye D, Yazdanbakhsh M (2008) Immune responses during helminth-malaria co-infection: a pilot study in Ghanaian school children. Parasitology 135 : 855–860. doi: 10.1017/S0031182008000401 18474122
12. Laranjeiras RF, Brant LC, Lima AC, Coelho PM, Braga EM (2008) Reduced protective effect of Plasmodium berghei immunization by concurrent Schistosoma mansoni infection. Mem Inst Oswaldo Cruz 103 : 674–677. 19057817
13. Tetsutani K, Ishiwata K, Torii M, Hamano S, Hisaeda H, et al. (2008) Concurrent infection with Heligmosomoides polygyrus modulates murine host response against Plasmodium berghei ANKA infection. Am J Trop Med Hyg 79 : 819–822. 19052285
14. Su Z, Segura M, Stevenson MM (2006) Reduced protective efficacy of a blood-stage malaria vaccine by concurrent nematode infection. Infect Immun 74 : 2138–2144. 16552043
15. Tetsutani K, Ishiwata K, Ishida H, Tu L, Torii M, et al. (2009) Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice. European journal of immunology 39 : 2822–2830. doi: 10.1002/eji.200939433 19728313
16. Knowles SC (2011) The effect of helminth co-infection on malaria in mice: a meta-analysis. Int J Parasitol 41 : 1041–1051. doi: 10.1016/j.ijpara.2011.05.009 21777589
17. Reynolds LA, Filbey KJ, Maizels RM (2012) Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus. Semin Immunopathol 34 : 829–846. doi: 10.1007/s00281-012-0347-3 23053394
18. Maizels RM, Hewitson JP, Murray J, Harcus YM, Dayer B, et al. (2012) Immune modulation and modulators in Heligmosomoides polygyrus infection. Exp Parasitol 132 : 76–89. doi: 10.1016/j.exppara.2011.08.011 21875581
19. Langhorne J, Gillard S, Simon B, Slade S, Eichmann K (1989) Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol 1 : 416–424. 2535135
20. Stephens R, Culleton RL, Lamb TJ (2012) The contribution of Plasmodium chabaudi to our understanding of malaria. Trends Parasitol 28 : 73–82. doi: 10.1016/j.pt.2011.10.006 22100995
21. Elias RM, Sardinha LR, Bastos KR, Zago CA, da Silva AP, et al. (2005) Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria. J Immunol 174 : 790–799. 15634900
22. Muxel SM, Freitas do Rosario AP, Zago CA, Castillo-Mendez SI, Sardinha LR, et al. (2011) The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PLoS One 6: e22434. doi: 10.1371/journal.pone.0022434 21814579
23. Cross CE, Langhorne J (1998) Plasmodium chabaudi chabaudi (AS): inflammatory cytokines and pathology in an erythrocytic-stage infection in mice. Exp Parasitol 90 : 220–229. 9806866
24. Murphy E, Shibuya K, Hosken N, Openshaw P, Maino V, et al. (1996) Reversibility of T helper 1 and 2 populations is lost after long-term stimulation. J Exp Med 183 : 901–913. 8642294
25. Grogan JL, Mohrs M, Harmon B, Lacy DA, Sedat JW, et al. (2001) Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14 : 205–215.
26. Zhu J, Min B, Hu-Li J, Watson CJ, Grinberg A, et al. (2004) Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 5 : 1157–1165. 15475959
27. Usui T, Preiss JC, Kanno Y, Yao ZJ, Bream JH, et al. (2006) T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203 : 755–766. 16520391
28. Krawczyk CM, Shen H, Pearce EJ (2007) Functional plasticity in memory T helper cell responses. J Immunol 178 : 4080–4088. 17371962
29. Peine M, Rausch S, Helmstetter C, Frohlich A, Hegazy AN, et al. (2013) Stable T-bet(+)GATA-3(+) Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation. PLoS Biol 11: e1001633. doi: 10.1371/journal.pbio.1001633 23976880
30. Coomes SM, Pelly VS, Wilson MS (2013) Plasticity within the alphabeta(+)CD4(+) T-cell lineage: when, how and what for? Open Biol 3 : 120157. doi: 10.1098/rsob.120157 23345540
31. Murphy KM, Stockinger B (2010) Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol 11 : 674–680. doi: 10.1038/ni.1899 20644573
32. O'Garra A, Gabrysova L, Spits H (2011) Quantitative events determine the differentiation and function of helper T cells. Nat Immunol 12 : 288–294. doi: 10.1038/ni.2003 21423225
33. Lohning M, Hegazy AN, Pinschewer DD, Busse D, Lang KS, et al. (2008) Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J Exp Med 205 : 53–61. doi: 10.1084/jem.20071855 18195073
34. Hegazy AN, Peine M, Helmstetter C, Panse I, Frohlich A, et al. (2010) Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity 32 : 116–128. doi: 10.1016/j.immuni.2009.12.004 20079668
35. Mohrs M, Shinkai K, Mohrs K, Locksley RM (2001) Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15 : 303–311. 11520464
36. Stetson DB, Mohrs M, Reinhardt RL, Baron JL, Wang ZE, et al. (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198 : 1069–1076. 14530376
37. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, et al. (2011) Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12 : 255–263. doi: 10.1038/ni.1993 21278737
38. Urban JF Jr., Katona IM, Finkelman FD (1991) Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice. Exp Parasitol 73 : 500–511. 1683629
39. Urban JF Jr., Katona IM, Paul WE, Finkelman FD (1991) Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci U S A 88 : 5513–5517. 2062833
40. Mastelic B, do Rosario AP, Veldhoen M, Renauld JC, Jarra W, et al. (2012) IL-22 Protects Against Liver Pathology and Lethality of an Experimental Blood-Stage Malaria Infection. Front Immunol 3 : 85. doi: 10.3389/fimmu.2012.00085 22566965
41. Min B, McHugh R, Sempowski GD, Mackall C, Foucras G, et al. (2003) Neonates support lymphopenia-induced proliferation. Immunity 18 : 131–140. 12530982
42. Ernst B, Lee DS, Chang JM, Sprent J, Surh CD (1999) The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11 : 173–181. 10485652
43. Bell EB, Sparshott SM, Drayson MT, Ford WL (1987) The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells. J Immunol 139 : 1379–1384. 3305705
44. Bourgeois C, Kassiotis G, Stockinger B (2005) A major role for memory CD4 T cells in the control of lymphopenia-induced proliferation of naive CD4 T cells. J Immunol 174 : 5316–5323. 15843528
45. Szabo SJ, Jacobson NG, Dighe AS, Gubler U, Murphy KM (1995) Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2 : 665–675. 7796298
46. Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185 : 817–824. 9120387
47. Usui T, Nishikomori R, Kitani A, Strober W (2003) GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 18 : 415–428. 12648458
48. Smeltz RB, Chen J, Ehrhardt R, Shevach EM (2002) Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression. Journal of immunology 168 : 6165–6172.
49. Remoue F, Diallo TO, Angeli V, Herve M, de Clercq D, et al. (2003) Malaria co-infection in children influences antibody response to schistosome antigens and inflammatory markers associated with morbidity. Trans R Soc Trop Med Hyg 97 : 361–364. 15228260
50. Mwangi TW, Bethony JM, Brooker S (2006) Malaria and helminth interactions in humans: an epidemiological viewpoint. Ann Trop Med Parasitol 100 : 551–570. 16989681
51. Salgame P, Yap GS, Gause WC (2013) Effect of helminth-induced immunity on infections with microbial pathogens. Nat Immunol 14 : 1118–1126. doi: 10.1038/ni.2736 24145791
52. Wilson S, Jones FM, Mwatha JK, Kimani G, Booth M, et al. (2008) Hepatosplenomegaly is associated with low regulatory and Th2 responses to schistosome antigens in childhood schistosomiasis and malaria coinfection. Infect Immun 76 : 2212–2218. doi: 10.1128/IAI.01433-07 18285496
53. Noland GS, Urban JF Jr., Fried B, Kumar N (2008) Counter-regulatory anti-parasite cytokine responses during concurrent Plasmodium yoelii and intestinal helminth infections in mice. Exp Parasitol 119 : 272–278. doi: 10.1016/j.exppara.2008.02.009 18396282
54. Helmby H, Kullberg M, Troye-Blomberg M (1998) Altered immune responses in mice with concomitant Schistosoma mansoni and Plasmodium chabaudi infections. Infect Immun 66 : 5167–5174. 9784518
55. Abdel-Wahab MF, Powers KG, Mahmoud SS, Good WC (1974) Suppression of schistosome granuloma formation by malaria in mice. Am J Trop Med Hyg 23 : 915–918. 4615597
56. Spence PJ, Langhorne J (2012) T cell control of malaria pathogenesis. Curr Opin Immunol 24 : 444–448. doi: 10.1016/j.coi.2012.05.003 22658628
57. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, et al. (2009) Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30 : 155–167. doi: 10.1016/j.immuni.2008.12.009 19144320
58. Helmby H (2009) Gastrointestinal nematode infection exacerbates malaria-induced liver pathology. Journal of immunology 182 : 5663–5671.
59. Wang YH, Voo KS, Liu B, Chen CY, Uygungil B, et al. (2010) A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med 207 : 2479–2491. doi: 10.1084/jem.20101376 20921287
60. Annunziato F, Cosmi L, Manetti R, Brugnolo F, Parronchi P, et al. (2001) Reversal of human allergen-specific CRTH2+ T(H)2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide. J Allergy Clin Immunol 108 : 815–821. 11692110
61. Levy Y, Thiebaut R, Montes M, Lacabaratz C, Sloan L, et al. (2014) Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load. Eur J Immunol.
62. Mahnke YD, Greenwald JH, DerSimonian R, Roby G, Antonelli LR, et al. (2012) Selective expansion of polyfunctional pathogen-specific CD4(+) T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome. Blood 119 : 3105–3112. doi: 10.1182/blood-2011-09-380840 22219223
63. Ding ZC, Huang L, Blazar BR, Yagita H, Mellor AL, et al. (2012) Polyfunctional CD4(+) T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy. Blood 120 : 2229–2239. doi: 10.1182/blood-2011-12-398321 22859605
64. Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, et al. (2007) Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 8 : 145–153. 17195845
65. Panzer M, Sitte S, Wirth S, Drexler I, Sparwasser T, et al. (2012) Rapid in vivo conversion of effector T cells into Th2 cells during helminth infection. J Immunol 188 : 615–623. doi: 10.4049/jimmunol.1101164 22156341
66. Williams CL, Schilling MM, Cho SH, Lee K, Wei M, et al. (2013) STAT4 and T-bet are required for the plasticity of IFN-gamma expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation. J Immunol 191 : 678–687. doi: 10.4049/jimmunol.1203360 23761633
67. Heath VL, Showe L, Crain C, Barrat FJ, Trinchieri G, et al. (2000) Cutting edge: ectopic expression of the IL-12 receptor-beta 2 in developing and committed Th2 cells does not affect the production of IL-4 or induce the production of IFN-gamma. J Immunol 164 : 2861–2865. 10706670
68. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, et al. (2002) T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3 : 549–557. 12006974
69. Fairlie-Clarke KJ, Lamb TJ, Langhorne J, Graham AL, Allen JE (2010) Antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity. BMC Immunol 11 : 6. doi: 10.1186/1471-2172-11-6 20163714
70. Naus CW, Jones FM, Satti MZ, Joseph S, Riley EM, et al. (2003) Serological responses among individuals in areas where both schistosomiasis and malaria are endemic: cross-reactivity between Schistosoma mansoni and Plasmodium falciparum. J Infect Dis 187 : 1272–1282. 12696007
71. Pierrot C, Wilson S, Lallet H, Lafitte S, Jones FM, et al. (2006) Identification of a novel antigen of Schistosoma mansoni shared with Plasmodium falciparum and evaluation of different cross-reactive antibody subclasses induced by human schistosomiasis and malaria. Infect Immun 74 : 3347–3354. 16714563
72. Sardinha LR, D'Imperio Lima MR, Alvarez JM (2002) Influence of the polyclonal activation induced by Plasmodium chabaudi on ongoing OVA-specific B - and T-cell responses. Scand J Immunol 56 : 408–416. 12234262
73. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, et al. (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378 : 88–91. 7477296
74. Kohno K, Kataoka J, Ohtsuki T, Suemoto Y, Okamoto I, et al. (1997) IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 158 : 1541–1550. 9029088
75. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, et al. (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68 : 869–877. 1547488
76. Madsen L, Labrecque N, Engberg J, Dierich A, Svejgaard A, et al. (1999) Mice lacking all conventional MHC class II genes. Proc Natl Acad Sci U S A 96 : 10338–10343. 10468609
77. Sinclair C, Bains I, Yates AJ, Seddon B (2013) Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system. Proc Natl Acad Sci U S A 110: E2905–2914. doi: 10.1073/pnas.1304859110 23858460
78. Barnden MJ, Allison J, Heath WR, Carbone FR (1998) Defective TCR expression in transgenic mice constructed using cDNA-based alpha - and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol 76 : 34–40. 9553774
79. Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, et al. (1994) Functional role of type I and type II interferons in antiviral defense. Science 264 : 1918–1921. 8009221
80. Shcherbo D, Murphy CS, Ermakova GV, Solovieva EA, Chepurnykh TV, et al. (2009) Far-red fluorescent tags for protein imaging in living tissues. The Biochemical journal 418 : 567–574. doi: 10.1042/BJ20081949 19143658
81. Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30 : 2114–2120. doi: 10.1093/bioinformatics/btu170 24695404
82. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, et al. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14: R36. doi: 10.1186/gb-2013-14-4-r36 23618408
83. Simon Anders PTP, Wolfgang Huber (2014) HTSeq—A Python framework to work with high-throughput sequencing data. bioRxiv preprint.
84. Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 : 139–140. doi: 10.1093/bioinformatics/btp616 19910308
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSSČlánek Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to MalariaČlánek Exploiting Fungal Virulence-Regulating Transcription Factors As Novel Antifungal Drug Targets
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Najčítanejšie v tomto čísle- RNA Virus Reassortment: An Evolutionary Mechanism for Host Jumps and Immune Evasion
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