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. 1983 Nov;42(2):708–715. doi: 10.1128/iai.42.2.708-715.1983

Participation of complement in host defense against capsule-deficient Haemophilus influenzae.

A Zwahlen, J A Winkelstein, E R Moxon
PMCID: PMC264487  PMID: 6605926

Abstract

To investigate the role of complement in immunity to capsule-deficient Haemophilus influenzae, rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule-deficient H. influenzae. Two of them (Rd and U1) did not elaborate type b capsular antigen, whereas the other (S2) elaborated 0.16% of the amount made by its type b parent strain. Depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule-deficient H. influenzae. After intraperitoneal inoculation with strain Rd or U1, C3-depleted rats developed bacteremia, whereas control rats did not; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3-depleted animals. To determine whether the greater virulence of strain S2, as compared with strain Rd or U1, was accounted for by the small amounts of capsular antigen it elaborated, we also compared its relative virulence to that of three genetically closely related capsule-deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen. No difference in virulence was observed among these four variants; all C3-depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates. These studies demonstrate a significant role for complement in host defense mechanisms against capsule-deficient H. influenzae and suggest that interstrain differences of virulence are not attributable to residual elaboration of small amounts of type b capsule.

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Selected References

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

  1. ALEXANDER H. E., LEIDY G. Determination of inherited traits of H. influenzae by desoxyribonucleic acid fractions isolated from type-specific cells. J Exp Med. 1951 Apr 1;93(4):345–359. doi: 10.1084/jem.93.4.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson P., Flesher A., Shaw S., Harding A. L., Smith D. H. Phenotypic and genetic variation in the susceptibility of Haemophilus influenzae type b to antibodies to somatic antigens. J Clin Invest. 1980 Apr;65(4):885–891. doi: 10.1172/JCI109741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson P., Johnston R. B., Jr, Smith D. H. Human serum activities against Hemophilus influenzae, type b. J Clin Invest. 1972 Jan;51(1):31–38. doi: 10.1172/JCI106793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barenkamp S. J., Munson R. S., Jr, Granoff D. M. Outer membrane protein and biotype analysis of pathogenic nontypable Haemophilus influenzae. Infect Immun. 1982 May;36(2):535–540. doi: 10.1128/iai.36.2.535-540.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barenkamp S. J., Munson R. S., Jr, Granoff D. M. Subtyping isolates of Haemophilus influenzae type b by outer-membrane protein profiles. J Infect Dis. 1981 May;143(5):668–676. doi: 10.1093/infdis/143.5.668. [DOI] [PubMed] [Google Scholar]
  6. Branefors P., Dahlberg T. Serum bactericidal effect on capsulated and non-capsulated Haemophilus influenzae. Acta Pathol Microbiol Scand C. 1980 Feb;88(1):47–56. doi: 10.1111/j.1699-0463.1980.tb00071.x. [DOI] [PubMed] [Google Scholar]
  7. Catlin B. W. Haemophilus influenzae in cultures of cerebrospinal fluid. Noncapsulated variants typable by immunofluorescence. Am J Dis Child. 1970 Sep;120(3):203–210. doi: 10.1001/archpedi.1970.02100080087005. [DOI] [PubMed] [Google Scholar]
  8. Corrall C. J., Winkelstein J. A., Moxon E. R. Participation of complement in host defense against encapsulated Haemophilus influenzae types a, c, and d. Infect Immun. 1982 Mar;35(3):759–763. doi: 10.1128/iai.35.3.759-763.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crosson F. J., Jr, Winkelstein J. A., Moxon E. R. Participation of complement in the nonimmune host defense against experimental Haemophilus influenzae type b septicemia and meningitis. Infect Immun. 1976 Oct;14(4):882–887. doi: 10.1128/iai.14.4.882-887.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flesher A. R., Insel R. A. Characterization of lipopolysaccharide of Haemophilus influenzae. J Infect Dis. 1978 Dec;138(6):719–730. doi: 10.1093/infdis/138.6.719. [DOI] [PubMed] [Google Scholar]
  11. Greene G. R. Meningitis due to Haemophilus influenzae other than type b: case report and review. Pediatrics. 1978 Dec;62(6):1021–1025. [PubMed] [Google Scholar]
  12. Hansen E. J., Frisch C. F., McDade R. L., Jr, Johnston K. H. Identification of immunogenic outer membrane proteins of Haemophilus influenzae type b in the infant rat model system. Infect Immun. 1981 Jun;32(3):1084–1092. doi: 10.1128/iai.32.3.1084-1092.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hansen E. J., Robertson S. M., Gulig P. A., Frisch C. F., Haanes E. J. Immunoprotection of rats against Haemophilus influenzae type B disease mediated by monoclonal antibody against a haemophilus outer-membrane protein. Lancet. 1982 Feb 13;1(8268):366–368. doi: 10.1016/s0140-6736(82)91394-0. [DOI] [PubMed] [Google Scholar]
  14. Loeb M. R., Smith D. H. Outer membrane protein composition in disease isolates of Haemophilus influenzae: pathogenic and epidemiological implications. Infect Immun. 1980 Dec;30(3):709–717. doi: 10.1128/iai.30.3.709-717.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lugtenberg B., Meijers J., Peters R., van der Hoek P., van Alphen L. Electrophoretic resolution of the "major outer membrane protein" of Escherichia coli K12 into four bands. FEBS Lett. 1975 Oct 15;58(1):254–258. doi: 10.1016/0014-5793(75)80272-9. [DOI] [PubMed] [Google Scholar]
  16. Marks M. I., Ziegler E. J., Douglas H., Corbeil L. B., Braude A. I. Induction of immunity against lethal Haemophilus influenzae type b infection by Escherichia coli core lipopolysaccharide. J Clin Invest. 1982 Apr;69(4):742–749. doi: 10.1172/JCI110512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. May J. R. Colonial morphology, antigens, and pathogenicity of Haemophilus influenzae. Sci Basis Med Annu Rev. 1967:211–226. [PubMed] [Google Scholar]
  18. Moxon E. R., Smith A. L., Averill D. R., Smith D. H. Haemophilus influenzae meningitis in infant rats after intranasal inoculation. J Infect Dis. 1974 Feb;129(2):154–162. doi: 10.1093/infdis/129.2.154. [DOI] [PubMed] [Google Scholar]
  19. Moxon E. R., Vaughn K. A. The type b capsular polysaccharide as a virulence determinant of Haemophilus influenzae: studies using clinical isolates and laboratory transformants. J Infect Dis. 1981 Apr;143(4):517–524. doi: 10.1093/infdis/143.4.517. [DOI] [PubMed] [Google Scholar]
  20. Musher D. M., Hague-Park M., Baughn R. E., Wallace R. J., Jr, Cowley B. Opsonizing and bactericidal effects of normal human serum on nontypable Haemophilus influenzae. Infect Immun. 1983 Jan;39(1):297–304. doi: 10.1128/iai.39.1.297-304.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pepple J., Moxon E. R., Yolken R. H. Indirect enzyme-linked immunosorbent assay for the quantitation of the type-specific antigen of Haemophilus influenzae b: a preliminary report. J Pediatr. 1980 Aug;97(2):233–237. doi: 10.1016/s0022-3476(80)80480-x. [DOI] [PubMed] [Google Scholar]
  22. Shaw S., Smith A. L., Anderson P., Smith D. H. The paradox of Hemophilus infuenzae type B bacteremia in the presence of serum bactericidal activity. J Clin Invest. 1976 Oct;58(4):1019–1029. doi: 10.1172/JCI108525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shin H. S., Mayer M. M. The third component of the guinea pig complement system. II. Kinetic study of the reaction of EAC'4,2a with guinea pig C'3. Enzymatic nature of C'3 comsumption, multiphasic character of fixation, and hemolytic titration of C'3. Biochemistry. 1968 Aug;7(8):2997–3002. doi: 10.1021/bi00848a041. [DOI] [PubMed] [Google Scholar]
  24. Shurin P. A., Pelton S. I., Tager I. B., Kasper D. L. Bactericidal antibody and susceptibility to otitis media caused by nontypable strains of Haemophilus influenzae. J Pediatr. 1980 Sep;97(3):364–369. doi: 10.1016/s0022-3476(80)80182-x. [DOI] [PubMed] [Google Scholar]
  25. Smith A. L., Smith D. H., Averill D. R., Jr, Marino J., Moxon E. R. Production of Haemophilus influenzae b meningitis in infant rats by intraperitoneal inoculation. Infect Immun. 1973 Aug;8(2):278–290. doi: 10.1128/iai.8.2.278-290.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sutton A., Schneerson R., Kendall-Morris S., Robbins J. B. Differential complement resistance mediates virulence of Haemophilus influenzae type b. Infect Immun. 1982 Jan;35(1):95–104. doi: 10.1128/iai.35.1.95-104.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tarr P. I., Hosea S. W., Brown E. J., Schneerson R., Sutton A., Frank M. M. The requirement of specific anticapsular IgG for killing of Haemophilus influenzae by the alternative pathway of complement activation. J Immunol. 1982 Apr;128(4):1772–1775. [PubMed] [Google Scholar]
  28. Tsai C. M., Frasch C. E. A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal Biochem. 1982 Jan 1;119(1):115–119. doi: 10.1016/0003-2697(82)90673-x. [DOI] [PubMed] [Google Scholar]
  29. Wallace R. J., Jr, Baker C. J., Quinones F. J., Hollis D. G., Weaver R. E., Wiss K. Nontypable Haemophilus influenzae (biotype 4) as a neonatal, maternal, and genital pathogen. Rev Infect Dis. 1983 Jan-Feb;5(1):123–136. doi: 10.1093/clinids/5.1.123. [DOI] [PubMed] [Google Scholar]
  30. Wallace R. J., Jr, Musher D. M., Septimus E. J., McGowan J. E., Jr, Quinones F. J., Wiss K., Vance P. H., Trier P. A. Haemophilus influenzae infections in adults: characterization of strains by serotypes, biotypes, and beta-lactamase production. J Infect Dis. 1981 Aug;144(2):101–106. doi: 10.1093/infdis/144.2.101. [DOI] [PubMed] [Google Scholar]
  31. Weller P. F., Smith A. L., Anderson P., Smith D. H. The role of encapsulation and host age in the clearance of Haemophilus influenzae bacteremia. J Infect Dis. 1977 Jan;135(1):34–41. doi: 10.1093/infdis/135.1.34. [DOI] [PubMed] [Google Scholar]
  32. Yogev R., Moxon E. R. Elaboration of type b capsule by Haemophilus influenzae as a determinant of pathogenicity and impaired killing by trimethoprim-sulfamethoxazole. J Clin Invest. 1982 Mar;69(3):658–665. doi: 10.1172/JCI110493. [DOI] [PMC free article] [PubMed] [Google Scholar]

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