Skip to main content

Advertisement

SpringerLink
Log in

Pneumocystis infection and the pathogenesis of chronic obstructive pulmonary disease

  • UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

With increases in the immunocompromised patient population and aging of the HIV+ population, the risk of serious fungal infections and their complications will continue to rise. In these populations, infection with the fungal opportunistic pathogen Pneumocystis jirovecii remains a leading cause of morbidity and mortality. Infection with Pneumocystis (Pc) has been shown to be associated with the development of chronic obstructive pulmonary disease (COPD) in human subjects with and without HIV infection and in non-human primate models of HIV infection. In human studies and in a primate model of HIV/Pc co-infection, we have shown that antibody response to the Pc protein, kexin (KEX1), correlates with protection from colonization, Pc pneumonia, and COPD. These findings support the hypothesis that immunity to KEX1 may be critical to controlling Pc colonization and preventing or slowing development of COPD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Bethesda, National Heart, Lung, and Blood Institute, April 2001; Update of the management sections. GOLD website (www.goldcopd.com).

  2. Snider GL. Chronic obstructive pulmonary disease: a definition and implications of structural determinants of airflow obstruction for epidemiology. Am Rev Respir Dis. 1989;140(3 Pt 2):S3–8.

    PubMed  CAS  Google Scholar 

  3. Barnes PJ. Mediators of chronic obstructive pulmonary disease. Pharmacol Rev. 2004;56(4):515–48.

    Article  PubMed  CAS  Google Scholar 

  4. Shapiro SD. Proteinases in chronic obstructive pulmonary disease. Biochem Soc Trans. 2002;30(2):98–102.

    Article  PubMed  CAS  Google Scholar 

  5. Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007;4(7):512–21.

    Article  PubMed  CAS  Google Scholar 

  6. Churg A, et al. Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release. Am J Respir Crit Care Med. 2003;167(8):1083–9.

    Article  PubMed  Google Scholar 

  7. Shapiro SD. The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160(5 Pt 2):S29–32.

    PubMed  CAS  Google Scholar 

  8. Taylor AE, et al. Defective macrophage phagocytosis of bacteria in COPD. Eur Respir J. 2010;35(5):1039–47.

    Article  PubMed  CAS  Google Scholar 

  9. Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med. 1997;155(2):449–53.

    PubMed  CAS  Google Scholar 

  10. Lacoste JY, et al. Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 1993;92(4):537–48.

    Article  PubMed  CAS  Google Scholar 

  11. O’Shaughnessy TC, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med. 1997;155(3):852–7.

    PubMed  Google Scholar 

  12. Hogg JC, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645–53.

    Article  PubMed  CAS  Google Scholar 

  13. Hogg JC. Role of latent viral infections in chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med. 2001;164(10 Pt 2):S71–5.

    PubMed  CAS  Google Scholar 

  14. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet. 2004;364(9435):709–21.

    Article  PubMed  Google Scholar 

  15. Morris A, Sciurba FC, Norris KA. Pneumocystis: a novel pathogen in chronic obstructive pulmonary disease? Copd. 2008;5(1):43–51.

    Article  PubMed  Google Scholar 

  16. Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest. 2000;117(5 Suppl 2):380S–5S.

    Article  PubMed  CAS  Google Scholar 

  17. Sethi S. Bacterial infection and the pathogenesis of COPD. Chest. 2000;117(5 Suppl 1):286S–91S.

    Article  PubMed  CAS  Google Scholar 

  18. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355–65.

    Article  PubMed  CAS  Google Scholar 

  19. Diaz PT, Clanton TL, Pacht ER. Emphysema-like pulmonary disease associated with human immunodeficiency virus infection. Ann Intern Med. 1992;116(2):124–8.

    PubMed  CAS  Google Scholar 

  20. Diaz O, et al. Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest. Eur Respir J. 2000;16(2):269–75.

    Article  PubMed  CAS  Google Scholar 

  21. Kuhlman JE, et al. Premature bullous pulmonary damage in AIDS: CT diagnosis. Radiology. 1989;173(1):23–6.

    PubMed  CAS  Google Scholar 

  22. Diaz PT, et al. HIV infection increases susceptibility to smoking-induced emphysema. Chest. 2000;117(5 Suppl 1):285S.

    Article  PubMed  Google Scholar 

  23. Gelman M, et al. Focal air trapping in patients with HIV infection: CT evaluation and correlation with pulmonary function test results. AJR Am J Roentgenol. 1999;172(4):1033–8.

    PubMed  CAS  Google Scholar 

  24. Diaz PT, et al. Respiratory symptoms among HIV-seropositive individuals. Chest. 2003;123(6):1977–82.

    Article  PubMed  Google Scholar 

  25. O’Donnell CR, et al. Abnormal airway function in individuals with the acquired immunodeficiency syndrome. Chest. 1988;94(5):945–8.

    Article  PubMed  Google Scholar 

  26. Crothers K, et al. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006;130(5):1326–33.

    Article  PubMed  Google Scholar 

  27. George MP, et al. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One. 2009;4(7):e6328.

    Article  PubMed  Google Scholar 

  28. Gingo MR, et al. Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era. Am J Respir Crit Care Med. 2010.

  29. Fernandes EF, et al. Colonization with Pneumocystis in a simian model of AIDS results in chronic inflammation and airflow obstruction. Am J Resp Crit Care Med. 2005;2:A867.

    Google Scholar 

  30. Morris A, et al. Relationship of Pneumocystis antibody response to severity of chronic obstructive pulmonary disease. Clin Infect Dis. 2008;47(7):e64–8.

    Article  PubMed  Google Scholar 

  31. Morris A, et al. Airway obstruction is increased in Pneumocystis-colonized human immunodeficiency virus-infected outpatients. J Clin Microbiol. 2009;47(11):3773–6.

    Article  PubMed  Google Scholar 

  32. Morris A, et al. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am J Respir Crit Care Med. 2004;170(4):408–13.

    Article  PubMed  Google Scholar 

  33. Morris AM, et al. Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus-infected persons. The pulmonary complications of HIV infection study group. Am J Respir Crit Care Med. 2000;162(2 Pt 1):612–6.

    PubMed  CAS  Google Scholar 

  34. Norris KA, et al. Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome. Immunol Res. 2006;36(1–3):175–87.

    Article  PubMed  CAS  Google Scholar 

  35. Shipley TW, et al. Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of AIDS. J Infect Dis. 2010;202(2):302–12.

    Article  PubMed  CAS  Google Scholar 

  36. Sing A, et al. Pneumocystis carinii carriage in immunocompetent patients with primary pulmonary disorders as detected by single or nested PCR. J Clin Microbiol. 1999;37(10):3409–10.

    PubMed  CAS  Google Scholar 

  37. Probst M, et al. Detection of Pneumocystis carinii DNA in patients with chronic lung diseases. Eur J Clin Microbiol Infect Dis. 2000;19(8):644–5.

    Article  PubMed  CAS  Google Scholar 

  38. Helweg-Larsen J, et al. Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia–a case-control study. BMC Infect Dis. 2002;2(1):28.

    Article  PubMed  Google Scholar 

  39. Calderon E, et al. Pneumocystis jiroveci isolates with dihydropteroate synthase mutations in patients with chronic bronchitis. Eur J Clin Microbiol Infect Dis. 2004;23(7):545–9.

    Article  PubMed  CAS  Google Scholar 

  40. Morris A, et al. Epidemiology and clinical significance of Pneumocystis colonization. J Infect Dis. 2008;197(1):10–7.

    Article  PubMed  CAS  Google Scholar 

  41. Morris A, et al. Prevalence and clinical predictors of Pneumocystis colonization among HIV-infected men. AIDS. 2004;18(5):793–8.

    Article  PubMed  Google Scholar 

  42. Board KF, et al. Experimental Pneumocystis carinii pneumonia in simian immunodeficiency virus-infected rhesus macaques. J Infect Dis. 2003;187(4):576–88.

    Article  PubMed  Google Scholar 

  43. Patil SP, et al. Immune responses to Pneumocystis colonization and infection in a simian model of AIDS. J Eukaryot Microbiol. 2003; 50 Suppl: 661–2.

    Google Scholar 

  44. Kling HM, et al. Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques. J Infect Dis. 2009;199(1):89–96.

    Article  PubMed  Google Scholar 

  45. Kling HM, et al. Relationship of Pneumocystis jiroveci humoral immunity to prevention of colonization and chronic obstructive pulmonary disease in a primate model of HIV infection. Infect Immun. 2010;78(10):4320–30.

    Article  PubMed  CAS  Google Scholar 

  46. Croix DA, et al. Alterations in T lymphocyte profiles of bronchoalveolar lavage fluid from SIV- and Pneumocystis carinii-coinfected rhesus macaques. AIDS Res Hum Retroviruses. 2002;18(5):391–401.

    Article  PubMed  Google Scholar 

  47. Joag SV. Primate models of AIDS. Microbes Infect. 2000;2(2):223–9.

    Article  PubMed  CAS  Google Scholar 

  48. George MP, et al. Pulmonary vascular lesions are common in SIV- and SHIV-env-infected macaques. AIDS Res Hum Retroviruses. 2010.

  49. Guillot J, et al. Phylogenetic relationships among Pneumocystis from Asian macaques inferred from mitochondrial rRNA sequences. Mol Phylogenet Evol. 2004;31(3):988–96.

    Article  PubMed  CAS  Google Scholar 

  50. Kling H, Shipley T, Norris K. Abnormalities in peripheral blood B lymphocyte populations in SHIV89.6P-infected macaques. Comp Med. 2011 (In press).

  51. Kuhrt D, et al. Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: rapid depletion of naive and memory B-cell subsets with delayed reconstitution of the naive B-cell population. J Virol. 2010;84(5):2466–76.

    Article  PubMed  CAS  Google Scholar 

  52. Morris A. Is there anything new in Pneumocystis jirovecii pneumonia? Changes in P. jirovecii pneumonia over the course of the AIDS epidemic. Clin Infect Dis. 2008;46(4):634–6.

    Article  PubMed  Google Scholar 

  53. Morris A, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004;10(10):1713–20.

    PubMed  Google Scholar 

  54. Empey KM, et al. Passive immunization of neonatal mice against Pneumocystis carinii f. sp. muris enhances control of infection without stimulating inflammation. Infect Immun. 2004;72(11):6211–20.

    Article  PubMed  CAS  Google Scholar 

  55. Lund FE, et al. B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J Immunol. 2006;176(10):6147–54.

    PubMed  CAS  Google Scholar 

  56. Lund FE, et al. Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P carinii-specific antibody. J Immunol. 2003;171(3):1423–30.

    PubMed  CAS  Google Scholar 

  57. Demanche C, et al. Molecular and serological evidence of Pneumocystis circulation in a social organization of healthy macaques (Macaca fascicularis). Microbiology. 2005;151(Pt 9):3117–25.

    Article  PubMed  CAS  Google Scholar 

  58. Zheng M, et al. CD4+ T cell-independent DNA vaccination against opportunistic infections. J Clin Invest. 2005;115(12):3536–44.

    Article  PubMed  CAS  Google Scholar 

  59. Wells J, et al. Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen. Infect Immun. 2006;74(4):2446–8.

    Article  PubMed  CAS  Google Scholar 

  60. Gingo MR, et al. Serologic responses to Pneumocystis proteins in human immunodeficiency virus patients with and without Pneumocystis jirovecii pneumonia. J Acquir Immune Defic Syndr. 2011.

Download references

Acknowledgments

This work was supported by NIH, National Heart Lung Blood Institute grants HL077095-05 and HL083432-05 (KAN); HL083461 and HL 090339 (AM).

Author information

Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, E 1057 Biomedical Science Tower, Pittsburgh, PA, 15261, USA

    Karen A. Norris & Alison Morris

  2. Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Alison Morris

Authors
  1. Karen A. Norris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alison Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karen A. Norris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norris, K.A., Morris, A. Pneumocystis infection and the pathogenesis of chronic obstructive pulmonary disease. Immunol Res 50, 175–180 (2011). https://doi.org/10.1007/s12026-011-8218-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-011-8218-x

Keywords

Search

Navigation