Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 Nov;61(11):4575–4581. doi: 10.1128/iai.61.11.4575-4581.1993

Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease.

H Lomholt 1, L van Alphen 1, M Kilian 1
PMCID: PMC281207  PMID: 8406854

Abstract

Considerable antigenic heterogeneity has been identified among Haemophilus influenzae immunoglobulin A1 (IgA1) proteases, and this study increases the number of antigenic types to more than 30. To address the role played in vivo by this polymorphism, sequential H. influenzae isolates from three healthy children and three patients with chronic obstructive pulmonary disease (COPD) were examined. Healthy children showed a frequent clonal exchange, with each replacing clone expressing an antigenic type of IgA1 protease not previously encountered. In contrast, COPD patients were colonized by a single clone for a significantly longer period. In one COPD clone, a change occurred in IgA1 protease cleavage specificity and antigenic properties. In conclusion, frequent exchange of clones expressing antigenically different IgA1 proteases seems to be the principal mechanism by which H. influenzae evades the immune response of healthy children against IgA1 protease. The results support the view that IgA1 protease activity is important for successful colonization of H. influenzae on mucosal membranes.

Full text

PDF
4575

Images in this article

4579Image
on p.4579
4579Image
on p.4579

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahl T., Reinholdt J. Detection of immunoglobulin A1 protease-induced Fab alpha fragments on dental plaque bacteria. Infect Immun. 1991 Feb;59(2):563–569. doi: 10.1128/iai.59.2.563-569.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brooks G. F., Lammel C. J., Blake M. S., Kusecek B., Achtman M. Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis. J Infect Dis. 1992 Dec;166(6):1316–1321. doi: 10.1093/infdis/166.6.1316. [DOI] [PubMed] [Google Scholar]
  3. Gilbert J. V., Plaut A. G., Longmaid B., Lamm M. E. Inhibition of microbial IgA proteases by human secretory IgA and serum. Mol Immunol. 1983 Sep;20(9):1039–1049. doi: 10.1016/0161-5890(83)90045-7. [DOI] [PubMed] [Google Scholar]
  4. Groeneveld K., van Alphen L., Eijk P. P., Jansen H. M., Zanen H. C. Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. J Infect Dis. 1988 Aug;158(2):360–365. doi: 10.1093/infdis/158.2.360. [DOI] [PubMed] [Google Scholar]
  5. Groeneveld K., van Alphen L., Voorter C., Eijk P. P., Jansen H. M., Zanen H. C. Antigenic drift of Haemophilus influenzae in patients with chronic obstructive pulmonary disease. Infect Immun. 1989 Oct;57(10):3038–3044. doi: 10.1128/iai.57.10.3038-3044.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Halter R., Pohlner J., Meyer T. F. Mosaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J. 1989 Sep;8(9):2737–2744. doi: 10.1002/j.1460-2075.1989.tb08415.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Higerd T. B., Virella G., Cardenas R., Koistinen J., Fett J. W. New method for obtaining IgA-specific protease. J Immunol Methods. 1977;18(3-4):245–249. doi: 10.1016/0022-1759(77)90178-8. [DOI] [PubMed] [Google Scholar]
  8. Kilian M., Mestecky J., Russell M. W. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol Rev. 1988 Jun;52(2):296–303. doi: 10.1128/mr.52.2.296-303.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kilian M., Thomsen B., Petersen T. E., Bleeg H. Molecular biology of Haemophilus influenzae IgA1 proteases. Mol Immunol. 1983 Sep;20(9):1051–1058. doi: 10.1016/0161-5890(83)90046-9. [DOI] [PubMed] [Google Scholar]
  10. Kobayashi K., Fujiyama Y., Hagiwara K., Kondoh H. Resistance of normal serum IgA and secretory IgA to bacterial IgA proteases: evidence for the presence of enzyme-neutralizing antibodies in both serum and secretory IgA, and also in serum IgG. Microbiol Immunol. 1987;31(11):1097–1106. doi: 10.1111/j.1348-0421.1987.tb01341.x. [DOI] [PubMed] [Google Scholar]
  11. Kuklinska D., Kilian M. Relative proportions of Haemophilus species in the throat of healthy children and adults. Eur J Clin Microbiol. 1984 Jun;3(3):249–252. doi: 10.1007/BF02014895. [DOI] [PubMed] [Google Scholar]
  12. Lomholt H., Poulsen K., Caugant D. A., Kilian M. Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2120–2124. doi: 10.1073/pnas.89.6.2120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mestecky J., Kilian M. Immunoglobulin A (IgA). Methods Enzymol. 1985;116:37–75. doi: 10.1016/s0076-6879(85)16005-2. [DOI] [PubMed] [Google Scholar]
  14. Murphy T. F., Apicella M. A. Nontypable Haemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection. Rev Infect Dis. 1987 Jan-Feb;9(1):1–15. doi: 10.1093/clinids/9.1.1. [DOI] [PubMed] [Google Scholar]
  15. Plaut A. G. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol. 1983;37:603–622. doi: 10.1146/annurev.mi.37.100183.003131. [DOI] [PubMed] [Google Scholar]
  16. Poulsen K., Hjorth J. P., Kilian M. Limited diversity of the immunoglobulin A1 protease gene (iga) among Haemophilus influenzae serotype b strains. Infect Immun. 1988 Apr;56(4):987–992. doi: 10.1128/iai.56.4.987-992.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poulsen K., Reinholdt J., Kilian M. A comparative genetic study of serologically distinct Haemophilus influenzae type 1 immunoglobulin A1 proteases. J Bacteriol. 1992 May;174(9):2913–2921. doi: 10.1128/jb.174.9.2913-2921.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reinholdt J., Krogh P., Holmstrup P. Degradation of IgA1, IgA2, and S-IgA by Candida and Torulopsis species. Acta Pathol Microbiol Immunol Scand C. 1987 Dec;95(6):265–274. doi: 10.1111/j.1699-0463.1987.tb00040.x. [DOI] [PubMed] [Google Scholar]
  19. Spinola S. M., Peacock J., Denny F. W., Smith D. L., Cannon J. G. Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study. J Infect Dis. 1986 Jul;154(1):100–109. doi: 10.1093/infdis/154.1.100. [DOI] [PubMed] [Google Scholar]
  20. Trottier S., Stenberg K., Svanborg-Edén C. Turnover of nontypable Haemophilus influenzae in the nasopharynges of healthy children. J Clin Microbiol. 1989 Oct;27(10):2175–2179. doi: 10.1128/jcm.27.10.2175-2179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES