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Serum Mannose-Binding Lectin Levels are Linked with Respiratory Syncytial Virus (RSV) Disease

Journal of Clinical Immunology volume 28, pages 166–173 (2008)Cite this article

Abstract

The innate immune response facilitates the quality of the adaptive immune response and is critical to an individual’s susceptibility to infection and disease. Mannose-binding lectin (MBL) is a plasma protein with anti-microbial properties that binds a wide range of pathogens to flag them for immune destruction independent of antibodies. In this study, serum MBL levels were measured in 81 children <5 years old experiencing acute respiratory syncytial virus infection and in 40 control children to determine the association with disease severity. Almost 70% of all RSV-infected children had low to intermediate MBL levels (<500 ng/ml) compared to controls, and most of the <6 months old RSV interned patients had low to intermediate levels. No differences were detected in MBL levels between case and control children <1 month old. Analysis of the T-cell compartment in peripheral blood mononuclear cells (PBMC) from acute RSV-infected and control children showed that the percent CD4+ T cells was statistically lower in RSV-infected children ≥6 months old compared to controls, while the percent CD8+ T cells in RSV-infected and control PBMC was generally similar. These results suggest that low serum MBL levels may be a marker of RSV disease severity in children and that MBL may be important in limiting RSV disease pathogenesis.

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References

  1. Hacimustafaoglu M, Celebi S, Aynaci E, Sinirtas M, Koksal N, Kucukerdogan A, et al. The progression of maternal RSV antibodies in the offspring. Arch Dis Child. 2004;89(1):52–3.

    Article  PubMed  CAS  Google Scholar 

  2. Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140(6):543–6.

    PubMed  CAS  Google Scholar 

  3. Palomo C, Cane PA, Melero JA. Evaluation of the antibody specificities of human convalescent-phase sera against the attachment (G) protein of human respiratory syncytial virus: influence of strain variation and carbohydrate side chains. J Med Virol. 2000;60(4):468–74.

    Article  PubMed  CAS  Google Scholar 

  4. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401.

    Article  PubMed  CAS  Google Scholar 

  5. Haynes LM, Moore DD, Kurt-Jones EA, Finberg RW, Anderson LJ, Tripp RA. Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol. 2001;75(22):10730–7.

    Article  PubMed  CAS  Google Scholar 

  6. Tripp RA. Pathogenesis of respiratory syncytial virus infection. Viral Immunol. 2004;17(2):165–81.

    Article  PubMed  CAS  Google Scholar 

  7. Harcourt J, Alvarez R, Jones LP, Henderson C, Anderson LJ, Tripp RA. Respiratory syncytial virus G protein and G protein CX3C motif adversely affect CX3CR1+T cell responses. J Immunol. 2006;176(3):1600–8.

    PubMed  CAS  Google Scholar 

  8. Tripp RA, Anderson LJ. Cytotoxic T-lymphocyte precursor frequencies in BALB/c mice after acute respiratory syncytial virus (RSV) infection or immunization with a formalin-inactivated RSV vaccine. J Virol. 1998;72(11):8971–5.

    PubMed  CAS  Google Scholar 

  9. Tripp RA, Dakhama A, Jones LP, Barskey A, Gelfand EW, Anderson LJ. The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P. J Virol. 2003;77(11):6580–4.

    Article  PubMed  CAS  Google Scholar 

  10. Tripp RA, Jones L, Anderson LJ. Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse. J Virol. 2000;74(13):6227–9.

    Article  PubMed  CAS  Google Scholar 

  11. Tripp RA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol. 2001;2(8):732–8.

    Article  PubMed  CAS  Google Scholar 

  12. Tripp RA, Moore D, Winter J, Anderson LJ. Respiratory syncytial virus infection and G and/or SH protein expression contribute to substance P, which mediates inflammation and enhanced pulmonary disease in BALB/c mice. J Virol. 2000;74(4):1614–22.

    Article  PubMed  CAS  Google Scholar 

  13. Haynes LM, Jones LP, Barskey A, Anderson LJ, Tripp RA. Enhanced disease and pulmonary eosinophilia associated with formalin-inactivated respiratory syncytial virus vaccination are linked to G glycoprotein CX3C-CX3CR1 interaction and expression of substance P. J Virol. 2003;77(18):9831–44.

    Article  PubMed  CAS  Google Scholar 

  14. Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol. 1969;89(4):405–21.

    PubMed  CAS  Google Scholar 

  15. Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969;89(4):449–63.

    PubMed  CAS  Google Scholar 

  16. de Graaff PM, Heidema J, Poelen MC, van Dijk ME, Lukens MV, van Gestel SP, et al. HLA-DP4 presents an immunodominant peptide from the RSV G protein to CD4 T cells. Virology. 2004;326(2):220–30.

    Article  PubMed  CAS  Google Scholar 

  17. Murphy BR, Walsh EE. Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity. J Clin Microbiol. 1988;26(8):1595–7.

    PubMed  CAS  Google Scholar 

  18. Piedra PA, Jewell AM, Cron SG, Atmar RL, Glezen WP. Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies. Vaccine. 2003;21(24):3479–82.

    Article  PubMed  Google Scholar 

  19. Queiróz DAO, Durigon EL, Botosso VF, Ejzemberg B, Vieira SE, Mineo JR, et al. Immune response to respiratory syncytial virus in young Brazilian children. Braz J Med Biol Res. 2002;35(10):1183–93.

    Article  PubMed  Google Scholar 

  20. van de Wetering JK, van Golde LM, Batenburg JJ. Collectins: players of the innate immune system. Eur J Biochem. 2004;271(7):1229–49.

    Article  PubMed  CAS  Google Scholar 

  21. Endo Y, Takahashi M, Fujita T. Lectin complement system and pattern recognition. Immunobiology. 2006;211(4):283–93.

    Article  PubMed  CAS  Google Scholar 

  22. Arnold JN, Dwek RA, Rudd PM, Sim RB. Mannan binding lectin and its interaction with immunoglobulins in health and in disease. Immunol Lett. 2006;106(2):103–10.

    Article  PubMed  CAS  Google Scholar 

  23. Gomi K, Tokue Y, Kobayashi T, Takahashi H, Watanabe A, Fujita T, et al. Mannose-binding lectin gene polymorphism is a modulating factor in repeated respiratory infections. Chest. 2004;126(1):95–9.

    Article  PubMed  CAS  Google Scholar 

  24. Cedzynski M, Szemraj J, Swierzko AS, Bak-Romaniszyn L, Banasik M, Zeman K, et al. Mannan-binding lectin insufficiency in children with recurrent infections of the respiratory system. Clin Exp Immunol. 2004;136(2):304–11.

    Article  PubMed  CAS  Google Scholar 

  25. Koch A, Melbye M, Sorensen P, Homoe P, Madsen HO, Molbak K, et al. Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. Jama. 2001;285(10):1316–21.

    Article  PubMed  CAS  Google Scholar 

  26. Bouwman LH, Roep BO, Roos A. Mannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol. 2006;67(4–5):247–56.

    Article  PubMed  CAS  Google Scholar 

  27. Casanova JL, Abel L. Human mannose-binding lectin in immunity: friend, foe, or both? J Exp Med. 2004;199(10):1295–9.

    Article  PubMed  CAS  Google Scholar 

  28. Davies J, Turner M, Klein N. The role of the collectin system in pulmonary defence. Paediatr Respir Rev. 2001;2(1):70–5.

    Article  PubMed  CAS  Google Scholar 

  29. Openshaw PJ, Tregoning JS. Immune responses and disease enhancement during respiratory syncytial virus infection. Clin Microbiol Rev. 2005;18(3):541–55.

    Article  PubMed  CAS  Google Scholar 

  30. Alwan WH, Kozlowska WJ, Openshaw PJ. Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med. 1994;179(1):81–9.

    Article  PubMed  CAS  Google Scholar 

  31. Hussell T, Baldwin CJ, O’Garra A, Openshaw PJ. CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection. Eur J Immunol. 1997;27(12):3341–9.

    Article  PubMed  CAS  Google Scholar 

  32. Gupta G, Surolia A. Collectins: sentinels of innate immunity. Bioessays. 2007;29(5):452–64.

    Article  PubMed  CAS  Google Scholar 

  33. Sorensen GL, Husby S, Holmskov U. Surfactant protein A and surfactant protein D variation in pulmonary disease. Immunobiology. 2007;212(4–5):381–416.

    Article  PubMed  CAS  Google Scholar 

  34. Azevedo AM, Durigon EL, Okasima V, Queiróz DAO, de Moraes-Vasconcelos D, Duarte AJ, et al. Detection of influenza, parainfluenza, adenovirus and respiratory syncytial virus during asthma attacks in children older than 2 years old. Allergol Immunopathol (Madr). 2003;31(6):311–7.

    Article  CAS  Google Scholar 

  35. Costa LF, Yokosawa J, Mantese OC, Oliveira TFM, Silveira HL, Nepomuceno LL, et al. Respiratory viruses in children younger than five years old with acute respiratory disease from 2001 to 2004 in Uberlandia, MG, Brazil. Mem Inst Oswaldo Cruz. 2006;101(3):301–6.

    Article  PubMed  CAS  Google Scholar 

  36. Peret TC, Hall CB, Hammond GW, Piedra PA, Storch GA, Sullender WM, et al. Circulation patterns of group A and B human respiratory syncytial virus genotypes in 5 communities in North America. J Infect Dis. 2000;181(6):1891–6.

    Article  PubMed  CAS  Google Scholar 

  37. Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006;43(1–2):86–96.

    Article  PubMed  CAS  Google Scholar 

  38. Salkind AR, McCarthy DO, Nichols JE, Domurat FM, Walsh EE, Roberts NJ Jr. Interleukin-1-inhibitor activity induced by respiratory syncytial virus: abrogation of virus-specific and alternate human lymphocyte proliferative responses. J Infect Dis. 1991;163(1):71–7.

    PubMed  CAS  Google Scholar 

  39. Azeredo EL, Zagne SM, Alvarenga AR, Nogueira RM, Kubelka CF, de Oliveira-Pinto LM. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease. Mem Inst Oswaldo Cruz. 2006;101(4):437–49.

    Article  PubMed  CAS  Google Scholar 

  40. Tripp RA, Moore D, Barskey At, Jones L, Moscatiello C, Keyserling H, et al. Peripheral blood mononuclear cells from infants hospitalized because of respiratory syncytial virus infection express T helper-1 and T helper-2 cytokines and CC chemokine messenger RNA. J Infect Dis. 2002;185(10):1388–94.

    Article  PubMed  CAS  Google Scholar 

  41. Moura FE, Borges LC, Portes SA, Ramos EA, Siqueira MM. Respiratory syncytial virus infections during an epidemic period in Salvador, Brazil. Viral antigenic group analysis and description of clinical and epidemiological aspects. Mem Inst Oswaldo Cruz. 2003;98(6):739–43.

    PubMed  Google Scholar 

  42. Takahashi K, Ip WE, Michelow IC, Ezekowitz RA. The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol. 2006;18(1):16–23.

    Article  PubMed  CAS  Google Scholar 

  43. Kristensen IA, Thiel S, Steffensen R, Madhi S, Sorour G, Olsen J. Mannan-binding lectin and RSV lower respiratory tract infection leading to hospitalization in children: a case-control study from Soweto, South Africa. Scand J Immunol. 2004;60(1–2):184–8.

    Article  PubMed  CAS  Google Scholar 

  44. Chagas KN, Steffensen R, Ferrao MSC, Dellanegra M, Duarte AS, Rutz R, et al. MBL2 gene and serum MBL levels in Brazilian children. Molecular Immunology. 2004;41(2–3):218–9.

    Google Scholar 

  45. Dean MM, Minchinton RM, Heatley S, Eisen DP. Mannose binding lectin acute phase activity in patients with severe infection. J Clin Immunol. 2005;25(4):346–52.

    Article  PubMed  CAS  Google Scholar 

  46. Becker Y. Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy—a review. Virus Genes. 2006;33(2):235–52.

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge the contributions of Dr. Dean D. Erdman, Centers for Disease Control and Prevention (CDC), Atlanta, GA, for providing some reagents; Fabiana R. Morais from Centro Regional de Hemoterapia, USP for her technical support; Ariadne Brito for collecting part of the control samples; the laboratories of Immunology, Molecular Biology, Parasitology, Physiology and Genetics, UFU and Centro Regional de Hemoterapia, USP, for their equipments; and the health care professionals of the Hospital de Clínicas for their important contribution.

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  1. Jonny Yokosawa

    Present address: NG Biotecnologia, Ltda, São Paulo, Brazil

Authors and Affiliations

  1. Laboratório de Virologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia (UFU), Av. Pará, 1720, Bloco 4C, andar superior, Campus Umuarama, 38400–902, Uberlândia, Minas Gerais, Brazil

    Lucas Zimon Giacomini Ribeiro, Lívia Maria Gonçalves Rossi, Thelma Fátima Mattos Oliveira, Lysa Luiz Nepomuceno & Divina Aparecida Oliveira Queiróz

  2. Center for Disease Intervention, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

    Ralph A. Tripp

  3. Hospital de Clínicas, UFU, Uberlândia, Minas Gerais, Brazil

    Orlando Cesar Mantese

  4. Centro Regional de Hemoterapia, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Patrícia Vianna Bonini Palma

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  1. Lucas Zimon Giacomini Ribeiro
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Correspondence to Divina Aparecida Oliveira Queiróz.

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Ribeiro, L.Z.G., Tripp, R.A., Rossi, L.M.G. et al. Serum Mannose-Binding Lectin Levels are Linked with Respiratory Syncytial Virus (RSV) Disease. J Clin Immunol 28, 166–173 (2008). https://doi.org/10.1007/s10875-007-9141-8

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Keywords

  • Respiratory syncytial virus
  • RSV
  • mannose-binding lectin
  • MBL