• 1.

    Babu S, Nutman TB, 2014. Immunology of lymphatic filariasis. Parasite Immunol 36: 338346.

  • 2.

    Nutman TB, 2013. Insights into the pathogenesis of disease in human lymphatic filariasis. Lymphat Res Biol 11: 144148.

  • 3.

    World Health Organization, 2017. Licence: CC BY-NC-SA 3.0 IGO. Guideline: Alternative Mass Drug Administration Regimens to Eliminate Lymphatic Filariasis. Geneva, Switzerland: WHO.

    • Search Google Scholar
    • Export Citation
  • 4.

    Owusu IO, Vroom FB, Mensah EO, Gyapong M, 2018. Elimination of lymphatic filariasis: current perspectives on mass drug administration. Res Rep Trop Med 9: 2533.

    • Search Google Scholar
    • Export Citation
  • 5.

    Allen JE, Maizels RM, 1996. Immunology of human helminth infection. Int Arch Allergy Immunol 109: 310.

  • 6.

    Jayaraman K, Ottesen EA, Nutman TB, King CL, Mahanty S, Kumaraswami V, Abrams JS, Regunathan J, 1993. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest 92: 16671673.

    • Search Google Scholar
    • Export Citation
  • 7.

    Mahanty S, Mollis SN, Ravichandran M, Abrams JS, Kumaraswami V, Jayaraman K, Ottesen EA, Nutman TB, 1996. High levels of spontaneous and parasite antigen-driven interieukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis. J Infect Dis 173: 769773.

    • Search Google Scholar
    • Export Citation
  • 8.

    Mahanty S, Nutman TB, 1995. Immunoregulation in human lymphatic filariasis: the role of interleukin 10. Parasite Immunol 17: 385392.

  • 9.

    Metenou S, Nutman TB, 2013. Regulatory T cell subsets in filarial infection and their function. Front Immunol 4: 18.

  • 10.

    Babu S, Blauvelt CP, Kumaraswami V, Nutman TB, 2005. Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation. J Immunol 175: 11701176.

    • Search Google Scholar
    • Export Citation
  • 11.

    Semnani RT et al. 2006. Filaria-induced monocyte dysfunction and its reversal following treatment. Infect Immun 74: 44094417.

  • 12.

    Babu S, Kumaraswami V, Nutman TB, 2009. Alternatively activated and immunoregulatory monocytes in human filarial infections. J Infect Dis 199: 18271837.

    • Search Google Scholar
    • Export Citation
  • 13.

    O’Regan NL, Steinfelder S, Venugopal G, Rao GB, Lucius R, Srikantam A, Hartmann S, 2014. Brugia malayi microfilariae induce a regulatory monocyte/macrophage phenotype that suppresses innate and adaptive immune responses. PLoS Negl Trop Dis 8: e3206.

    • Search Google Scholar
    • Export Citation
  • 14.

    Brown JA, Dorfman DM, Ma F-R, Sullivan EL, Munoz O, Wood CR, Greenfield Ea, Freeman GJ, 2003. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 170: 12571266.

    • Search Google Scholar
    • Export Citation
  • 15.

    Freeman GJ et al. 2000. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192: 10271034.

    • Search Google Scholar
    • Export Citation
  • 16.

    Keir ME, Butte MJ, Freeman GJ, Sharpe AH, 2008. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26: 677704.

  • 17.

    Bardhan K, Anagnostou T, Boussiotis VA, 2016. The PD1:PD-L1/2 pathway from discovery to clinical implementation. Front Immunol 7: 550.

  • 18.

    Latchman Y et al. 2001. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2: 261268.

  • 19.

    Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ, 2007. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27: 111122.

    • Search Google Scholar
    • Export Citation
  • 20.

    Wilcox RA et al. 2009. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood 114: 21492158.

  • 21.

    Keir ME, Francisco LM, Sharpe AH, 2007. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol 19: 309314.

  • 22.

    Asadullah K, Sterry W, Volk HD, 2003. Interleukin-10 therapy—review of a new approach. Med Immunol 55: 241269.

  • 23.

    de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE, 1991. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174: 12091220.

    • Search Google Scholar
    • Export Citation
  • 24.

    Akdis CA, Blaser K, 2001. Mechanisms of interleukin-10-mediated immune suppression. Immunology 103: 131136.

  • 25.

    Mosser DM, Zhang X, 2008. Interleukin 10: new perspectives on an old cytokines. Immunol Rev 226: 205218.

  • 26.

    Metenou S et al. 2010. At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells. J Immunol 184: 53755382.

    • Search Google Scholar
    • Export Citation
  • 27.

    Metenou S et al. 2009. Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population. J Immunol 183: 916924.

    • Search Google Scholar
    • Export Citation
  • 28.

    Ravichandran M, Mahanty S, Kumaraswami V, Nutman TB, Jayaraman K, 1997. Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection. Parasite Immunol 19: 6977.

    • Search Google Scholar
    • Export Citation
  • 29.

    Choi EH, Nutman TB, Chanock SJ, 2003. Genetic variation in immune function and susceptibility to human filariasis. Expert Rev Mol Diagn 3: 367374.

    • Search Google Scholar
    • Export Citation
  • 30.

    Figueiredo CA et al. 2013. Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil. J Allergy Clin Immunol 131: 16831690.

    • Search Google Scholar
    • Export Citation
  • 31.

    Assis S, Marques CR, Silva TM, Costa RS, Alcantara-Neves NM, Barreto ML, Barnes KC, Figueiredo CA, 2014. IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection. Helicobacter 19: 168173.

    • Search Google Scholar
    • Export Citation
  • 32.

    Saxena M, Srivastava N, Banerjee M, 2013. Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus. Mol Biol Rep 40: 62716279.

    • Search Google Scholar
    • Export Citation
  • 33.

    Zheng XY, Guan WJ, Mao C, Chen HF, Ding H, Zheng JP, Hu TT, Luo MH, Huang YH, Chen Q, 2014. Interleukin-10 promoter 1082/-819/-592 polymorphisms are associated with asthma susceptibility in Asians and atopic asthma: a meta-analysis. Lung 192: 6573.

    • Search Google Scholar
    • Export Citation
  • 34.

    Zhang YM, Zhou XC, Xu Z, Tang CJ, 2012. Meta-analysis of epidemiological studies of association of two polymorphisms in the interleukin-10 gene promoter and colorectal cancer risk. Genet Mol Res 11: 33893397.

    • Search Google Scholar
    • Export Citation
  • 35.

    Dai ZJ, Wang XJ, Zhao Y, Ma XB, Kang HF, Min WL, Lin S, Yang PT, Liu XX, 2014. Effects of interleukin-10 polymorphisms (rs1800896, rs1800871, and rs1800872) on breast cancer risk: evidence from an updated meta-analysis. Genet Test Mol Biomarkers 18: 439445.

    • Search Google Scholar
    • Export Citation
  • 36.

    Ben-Selma W, Ben-Abderrahmen Y, Boukadida J, Harizi H, 2012. IL-10R1 S138G loss-of-function polymorphism is associated with extrapulmonary tuberculosis risk development in Tunisia. Mol Biol Rep 39: 5156.

    • Search Google Scholar
    • Export Citation
  • 37.

    Hikami K, Ehara Y, Hasegawa M, Fujimoto M, Matsushita M, Oka T, Takehara K, Sato S, Tokunaga K, Tsuchiya N, 2008. Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis. Biochem Biophys Res Commun 373: 403407.

    • Search Google Scholar
    • Export Citation
  • 38.

    Peng H, Liu CY, Zhou M, Wen PF, Zhang M, Qiu LJ, Ni J, Liang Y, Pan HF, Ye DQ, 2013. IL-10RB rs2834167 (A/G) polymorphism is associated with the susceptibility to systemic lupus erythematosus: evidence from a study in Chinese Han population. Inflammation 36: 12181224.

    • Search Google Scholar
    • Export Citation
  • 39.

    Yoo KH, Kim SK, Chung JH, Chang SG, 2011. Association of IL10, IL10RA, and IL10RB polymorphisms with benign prostate hyperplasia in Korean population. J Korean Med Sci 26: 659664.

    • Search Google Scholar
    • Export Citation
  • 40.

    Park HK, Kim DH, Yun DH, Ban JY, 2013. Association between IL10, IL10RA, and IL10RB SNPs and ischemic stroke with hypertension in Korean population. Mol Biol Rep 40: 17851790.

    • Search Google Scholar
    • Export Citation
  • 41.

    Lee SH et al. 2006. Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population. Arthritis Res Ther 8: R163.

    • Search Google Scholar
    • Export Citation
  • 42.

    Huang CH, Wong RH, Wei JCC, Tsay MD, Chen WC, Chen HY, Shih WT, Chiou SP, Tu YC, Lee HS, 2011. Effects of genetic polymorphisms of programmed cell death 1 and its ligands on the development of ankylosing spondylitis. Rheumatology 50: 18091813.

    • Search Google Scholar
    • Export Citation
  • 43.

    Ren HT et al. 2016. PD-1 rs2227982 polymorphism is associated with the decreased risk of breast cancer in northwest Chinese women. Medicine (Baltimore) 95: e3760.

    • Search Google Scholar
    • Export Citation
  • 44.

    Zhou RM, Li Y, Wang N, Huang X, Cao SR, Shan BE, 2016. Association of programmed death-1 polymorphisms with the risk and prognosis of esophageal squamous cell carcinoma. Cancer Genet 209: 365375.

    • Search Google Scholar
    • Export Citation
  • 45.

    Wang W, Li F, Mao Y, Zhou H, Sun J, Li R, Liu C, Chen W, Hua D, Zhang X, 2013. A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma. Hum Genet 132: 641648.

    • Search Google Scholar
    • Export Citation
  • 46.

    Pizarro C, García-Díaz DF, Codner E, Salas-Pérez F, Carrasco E, Pérez-Bravo F, 2014. PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile. Diabetes Metab Res Rev 30: 761766.

    • Search Google Scholar
    • Export Citation
  • 47.

    Tao LH et al. 2017. A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer. Cancer Immunol Immunother 66: 309318.

    • Search Google Scholar
    • Export Citation
  • 48.

    Lee SY et al. 2017. Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer. Gene 599: 2835.

    • Search Google Scholar
    • Export Citation
  • 49.

    Wang SC, Lin CH, Ou TT, Wu CC, Tsai WC, 2007. Ligands for programmed cell death 1 gene in patients with systemic lupus erythematosus. J Rheumatol 34: 721725.

    • Search Google Scholar
    • Export Citation
  • 50.

    Debrah AY, Batsa L, Albers A, Mand S, Toliat MR, Nürnberg P, Adjei O, Hoerauf A, Pfarr K, 2011. Transforming growth factor-β1 variant Leu10Pro is associated with both lack of microfilariae and differential microfilarial loads in the blood of persons infected with lymphatic filariasis. Hum Immunol 72: 11431148.

    • Search Google Scholar
    • Export Citation
  • 51.

    Choi EH, Zimmerman PA, Foster CB, Zhu S, Kumaraswami V, Nutman TB, Chanock SJ, 2001. Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in south India. Genes Immun 2: 248253.

    • Search Google Scholar
    • Export Citation
  • 52.

    Hise A, Hazlett F, Bockarie M, Zimmerman P, Tisch D, Kazura J, 2003. Polymorphisms of innate immunity genes and susceptibility to lymphatic filariasis. Genes Immun 4: 524527.

    • Search Google Scholar
    • Export Citation
  • 53.

    Idris ZM, Miswan N, Muhi J, Mohd TA, Kun JF, Noordin R, 2011. Association of CTLA4 gene polymorphisms with lymphatic filariasis in an east Malaysian population. Hum Immunol 72: 607612.

    • Search Google Scholar
    • Export Citation
  • 54.

    Debrah AY, Mand S, Toliat MR, Marfo-Debrekyei Y, Batsa L, Nürnberg P, Lawson B, Adjei O, Hoerauf A, Pfarr K, 2007. Plasma vascular endothelial growth factor-A (VEGF-A) and VEGF-A gene polymorphism are associated with hydrocele development in lymphatic filariasis. Am J Trop Med Hyg 77: 601608.

    • Search Google Scholar
    • Export Citation
  • 55.

    Chan SH, Dissanayake S, Mak JW, Ismail MM, Wee GB, Srinivasan N, Soo BH, Zaman V, 1984. HLA and filariasis in Sri Lankans and Indians. Southeast Asian J Trop Med Public Health 15: 281286.

    • Search Google Scholar
    • Export Citation
  • 56.

    Hoerauf A, Kruse S, Brattig NW, Heinzmann A, Mueller-Myhsok B, Deichmann KA, 2002. The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda). Microbes Infect 4: 3742.

    • Search Google Scholar
    • Export Citation
  • 57.

    Aggarwal S, Ali S, Chopra R, Srivastava A, Kalaiarasan P, Malhotra D, Gochhait S, Garg VK, Bhattacharya SN, Bamezai RN, 2011. Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform. J Infect Dis 204: 12641273.

    • Search Google Scholar
    • Export Citation
  • 58.

    Ramaseri Sunder S, Hanumanth SR, Nagaraju RT, Neela Venkata SK, Suryadevara NC, Pydi SS, Gaddam S, Jonnalagada S, Valluri VL, 2012. IL-10 high producing genotype predisposes HIV infected individuals to TB infection. Hum Immunol 73: 605611.

    • Search Google Scholar
    • Export Citation
  • 59.

    Zhang G et al. 2012. Interleukin-10 (IL-10) polymorphisms are associated with IL-10: production and clinical malaria in young children. Infect Immun 80: 23162322.

    • Search Google Scholar
    • Export Citation
  • 60.

    Li J, Liu Y, Xu F, Chen J, Chen Y, 2013. Three polymorphisms in the IL-10 gene and the risk of HCV infection: a meta-analysis plus a Chinese association study involving 1140 subjects. Epidemiol Infect 141: 893904.

    • Search Google Scholar
    • Export Citation
  • 61.

    Hussain SK, Madeleine MM, Johnson LG, Du Q, Galloway DA, Daling JR, Malkki M, Petersdorf EW, Schwartz SM, 2013. Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and case-control study. Int J Cancer 133: 201213.

    • Search Google Scholar
    • Export Citation
  • 62.

    Yamazaki T et al. 2002. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol 169: 55385545.

  • 63.

    Saunders PA, Hendrycks VR, Lidinsky WA, Woods ML, 2005. PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion. Eur J Immunol 35: 35613569.

    • Search Google Scholar
    • Export Citation
  • 64.

    Riella C, Paterson AM, Sharpe AH, Chandraker A, 2012. Role of the PD-1 pathway in the immune response. Am J Transplant 12: 25752587.

  • 65.

    Lewkowich IP, Lajoie S, Stoffers SL, Suzuki Y, Richgels PK, Dienger K, Sproles AA, Yagita H, Hamid Q, Wills-Karp M, 2013. PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production. Mucosal Immunol 6: 728739.

    • Search Google Scholar
    • Export Citation
  • 66.

    Colley DG, Sasser LE, Reed AM, 2005. PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity. Parasite Immunol 27: 4553.

    • Search Google Scholar
    • Export Citation
  • 67.

    Loke P, Allison JP, 2003. PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Proc Natl Acad Sci USA 100: 53365341.

  • 68.

    Lázár-Molnár E, Yan Q, Cao E, Ramagopal U, Nathenson SG, Almo SC, 2008. Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. Proc Natl Acad Sci USA 105: 1048310488.

    • Search Google Scholar
    • Export Citation
  • 69.

    Ghiotto M, Gauthier L, Serriari N, Pastor S, Truneh A, Nunès JA, Olive D, 2010. PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1. Int Immunol 22: 651660.

    • Search Google Scholar
    • Export Citation
  • 70.

    Carter LL et al. 2007. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol 182: 124134.

    • Search Google Scholar
    • Export Citation
  • 71.

    Karunarathne DS et al. 2016. Programmed death-1 ligand 2-mediated regulation of the PD-L1 to PD-1 axis is essential for establishing CD4+ T cell immunity. Immunity 45: 333345.

    • Search Google Scholar
    • Export Citation
  • 72.

    Xiao Y et al. 2014. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 211: 943959.

    • Search Google Scholar
    • Export Citation
  • 73.

    Chen L, Han X, 2015. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 125: 33843391.

 
 
 

 

 
 
 

 

 

 

 

 

 

Association of a PD-L2 Gene Polymorphism with Chronic Lymphatic Filariasis in a South Indian Cohort

View More View Less
  • 1 Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany;
  • | 2 National Institutes of Health, National Institute of Research in Tuberculosis (NIRT), International Centre for Excellence in Research, Chennai, India;
  • | 3 Institute for Microbiology and Hygiene, Charité–Universitätsmedizin Berlin, Berlin, Germany;
  • | 4 Blue Peter Public Health and Research Centre, LEPRA Society, Hyderabad, India;
  • | 5 Department of Veterinary Medicine, Institute for Veterinary Epidemiology and Biostatistics, Freie Universität Berlin, Berlin, Germany;
  • | 6 Department of Neural Circuits and Behavior, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy–Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957–9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.

Author Notes

Address correspondence to Svenja Steinfelder, Department of Neural Circuits and Behavior, Max Delbrück Center for Molecular Medicine, NWFZ, Charitéplatz 1, Berlin 10117, Germany. E-mail: svenja.steinfelder@mdc-berlin.de

Authors’ addresses: Gopinath Venugopal, Noëlle L. O’Regan, and Susanne Hartmann, Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany, E-mails: gopinath.v@fu-berlin.de, noelleoregan@gmail.com, and susanne.hartmann@fu-berlin.de. Subash Babu, National Institutes of Health, National Institute of Research in Tuberculosis (NIRT), International Center for Excellence in Research, Chennai, India, E-mail: sbabu@mail.nih.gov. Ralf R. Schumann, Institut für Mikrobiologie, Charité–Universitätsmedizin, Berlin, Germany, E-mail: ralf.schumann@charite.de. Aparna Srikantam, Blue Peter Public Health and Research Center, LEPRA Society, Hyderabad, India, E-mail: aparna@leprahealthinaction.in. Roswitha Merle, Department of Veterinary Medicine, Institute of Veterinary Epidemiology and Biometry, Epidemiology Group, Freie Universität Berlin, Berlin, Germany, E-mail: roswitha.merle@fu-berlin.de. Svenja Steinfelder, Department of Neural Circuits and Behavior, Max Delbrück Center for Molecular Medicine, Berlin, Germany, E-mail: svenja.steinfelder@mdc-berlin.de.

Save