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. 1995 Aug;63(8):2818–2825. doi: 10.1128/iai.63.8.2818-2825.1995

Clearance of Pseudomonas aeruginosa from the murine gastrointestinal tract is effectively mediated by O-antigen-specific circulating antibodies.

G B Pier 1, G Meluleni 1, J B Goldberg 1
PMCID: PMC173382  PMID: 7542632

Abstract

The colonization of mucosal surfaces by Pseudomonas aeruginosa can lead to local or disseminated disease. Secretory immunoglobulin A (IgA) has been assumed to be responsible for preventing mucosal colonization by interfering with the binding of bacterial ligands to epithelial surface receptors. However, the efficacy of this mechanism of immunity derives little actual support from in vivo experiments. In an investigation of the role of local and systemic immunization strategies in reducing colonization of the gastrointestinal tract of mice by P. aeruginosa, the bacterial antigens that were potential targets for immune effectors promoting mucosal clearance were identified. Levels of gastrointestinal colonization were reduced when immunity to homologous O antigens, but not that to pili or flagella, was elicited. Oral vaccination with attenuated Salmonella typhimurium expressing P. aeruginosa serogroup O11 antigen elicited mucosal and serum IgA antibodies and serum IgG antibodies specific for the recombinant antigen. Oral challenge of immunized mice with P. aeruginosa serogroup O11 demonstrated protection against gastrointestinal colonization. Intraperitoneal immunization with a serogroup O11 high-molecular-weight O-polysaccharide antigen elicited only serum IgG and IgM antibodies yet was as effective as oral vaccination in protecting mice against gastrointestinal colonization. This finding was confirmed by the demonstration that intraperitoneal immunization with purified lipopolysaccharide was also protective against mucosal surface colonization. These results call into question the need for local immune effectors, particularly secretory IgA, directed at bacterial ligands for epithelial surface components, in protecting a mucosal surface from bacterial challenge.

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Selected References

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  1. Andremont A., Marang B., Tancrède C., Baume D., Hill C. Antibiotic treatment and intestinal colonization by Pseudomonas aeruginosa in cancer patients. Antimicrob Agents Chemother. 1989 Aug;33(8):1400–1402. doi: 10.1128/aac.33.8.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Attridge S. Oral immunization with Salmonella typhi Ty21a-based clones expressing Vibrio cholerae O-antigen: serum bactericidal antibody responses in man in relation to pre-immunization antibody levels. Vaccine. 1991 Dec;9(12):877–882. doi: 10.1016/0264-410x(91)90007-s. [DOI] [PubMed] [Google Scholar]
  3. Avery V. M., Gordon D. L. Antibacterial properties of breast milk: requirements for surface phagocytosis and chemiluminescence. Eur J Clin Microbiol Infect Dis. 1991 Dec;10(12):1034–1039. doi: 10.1007/BF01984925. [DOI] [PubMed] [Google Scholar]
  4. Banerjee S. N., Emori T. G., Culver D. H., Gaynes R. P., Jarvis W. R., Horan T., Edwards J. R., Tolson J., Henderson T., Martone W. J. Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System. Am J Med. 1991 Sep 16;91(3B):86S–89S. doi: 10.1016/0002-9343(91)90349-3. [DOI] [PubMed] [Google Scholar]
  5. Bessen D., Fischetti V. A. Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci. Infect Immun. 1988 Oct;56(10):2666–2672. doi: 10.1128/iai.56.10.2666-2672.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bessen D., Fischetti V. A. Passive acquired mucosal immunity to group A streptococci by secretory immunoglobulin A. J Exp Med. 1988 Jun 1;167(6):1945–1950. doi: 10.1084/jem.167.6.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bessen D., Fischetti V. A. Synthetic peptide vaccine against mucosal colonization by group A streptococci. I. Protection against a heterologous M serotype with shared C repeat region epitopes. J Immunol. 1990 Aug 15;145(4):1251–1256. [PubMed] [Google Scholar]
  8. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Boukadida J., de Montalembert M., Gaillard J. L., Gobin J., Grimont F., Girault D., Véron M., Berche P. Outbreak of gut colonization by Pseudomonas aeruginosa in immunocompromised children undergoing total digestive decontamination: analysis by pulsed-field electrophoresis. J Clin Microbiol. 1991 Sep;29(9):2068–2071. doi: 10.1128/jcm.29.9.2068-2071.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bourguin I., Chardes T., Mevelec M. N., Woodman J. P., Bout D. Amplification of the secretory IgA response to Toxoplasma gondii using cholera toxin. FEMS Microbiol Lett. 1991 Jul 1;65(3):265–271. doi: 10.1016/0378-1097(91)90225-y. [DOI] [PubMed] [Google Scholar]
  11. Boyer H. W., Roulland-Dussoix D. A complementation analysis of the restriction and modification of DNA in Escherichia coli. J Mol Biol. 1969 May 14;41(3):459–472. doi: 10.1016/0022-2836(69)90288-5. [DOI] [PubMed] [Google Scholar]
  12. Bronze M. S., Courtney H. S., Dale J. B. Epitopes of group A streptococcal M protein that evoke cross-protective local immune responses. J Immunol. 1992 Feb 1;148(3):888–893. [PubMed] [Google Scholar]
  13. Bronze M. S., McKinsey D. S., Beachey E. H., Dale J. B. Protective immunity evoked by locally administered group A streptococcal vaccines in mice. J Immunol. 1988 Oct 15;141(8):2767–2770. [PubMed] [Google Scholar]
  14. Böttiger M. Long-term immunity following vaccination with killed poliovirus vaccine in Sweden, a country with no circulating poliovirus. Rev Infect Dis. 1984 May-Jun;6 (Suppl 2):S548–S551. doi: 10.1093/clinids/6.supplement_2.s548. [DOI] [PubMed] [Google Scholar]
  15. Carlsen K. H., Mellbye O. J., Fuglerud P., Johansen B., Solheim A. B., Belsnes D., Danielsen A., Henrichson L. Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants. Pediatr Allergy Immunol. 1993 Feb;4(1):20–25. doi: 10.1111/j.1399-3038.1993.tb00060.x. [DOI] [PubMed] [Google Scholar]
  16. Collins H. H., Cross A. S., Dobek A., Opal S. M., McClain J. B., Sadoff J. C. Oral ciprofloxacin and a monoclonal antibody to lipopolysaccharide protect leukopenic rats from lethal infection with Pseudomonas aeruginosa. J Infect Dis. 1989 Jun;159(6):1073–1082. doi: 10.1093/infdis/159.6.1073. [DOI] [PubMed] [Google Scholar]
  17. Cross A. S., Opal S. M., Palardy J. E., Bodmer M. W., Sadoff J. C. The efficacy of combination immunotherapy in experimental Pseudomonas sepsis. J Infect Dis. 1993 Jan;167(1):112–118. doi: 10.1093/infdis/167.1.112. [DOI] [PubMed] [Google Scholar]
  18. Curtiss R., 3rd, Kelly S. M. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect Immun. 1987 Dec;55(12):3035–3043. doi: 10.1128/iai.55.12.3035-3043.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Czinn S. J., Nedrud J. G. Oral immunization against Helicobacter pylori. Infect Immun. 1991 Jul;59(7):2359–2363. doi: 10.1128/iai.59.7.2359-2363.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. DeBaets F., Kint J., Pauwels R., Leroy J. IgG subclass deficiency in children with recurrent bronchitis. Eur J Pediatr. 1992 Apr;151(4):274–278. doi: 10.1007/BF02072228. [DOI] [PubMed] [Google Scholar]
  21. Deitch E. A., Xu D. Z., Qi L., Berg R. D. Bacterial translocation from the gut impairs systemic immunity. Surgery. 1991 Mar;109(3 Pt 1):269–276. [PubMed] [Google Scholar]
  22. Figurski D. H., Helinski D. R. Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1648–1652. doi: 10.1073/pnas.76.4.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Fischetti V. A., Hodges W. M., Hruby D. E. Protection against streptococcal pharyngeal colonization with a vaccinia: M protein recombinant. Science. 1989 Jun 23;244(4911):1487–1490. doi: 10.1126/science.2660266. [DOI] [PubMed] [Google Scholar]
  24. Friedman A. M., Long S. R., Brown S. E., Buikema W. J., Ausubel F. M. Construction of a broad host range cosmid cloning vector and its use in the genetic analysis of Rhizobium mutants. Gene. 1982 Jun;18(3):289–296. doi: 10.1016/0378-1119(82)90167-6. [DOI] [PubMed] [Google Scholar]
  25. Glass R. I., Svennerholm A. M., Khan M. R., Huda S., Huq M. I., Holmgren J. Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection. J Infect Dis. 1985 Feb;151(2):236–242. doi: 10.1093/infdis/151.2.236. [DOI] [PubMed] [Google Scholar]
  26. Goldberg J. B., Hatano K., Meluleni G. S., Pier G. B. Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10716–10720. doi: 10.1073/pnas.89.22.10716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hatano K., Boisot S., DesJardins D., Wright D. C., Brisker J., Pier G. B. Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa. Infect Immun. 1994 Sep;62(9):3608–3616. doi: 10.1128/iai.62.9.3608-3616.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hatano K., Goldberg J. B., Pier G. B. Pseudomonas aeruginosa lipopolysaccharide: evidence that the O side chains and common antigens are on the same molecule. J Bacteriol. 1993 Aug;175(16):5117–5128. doi: 10.1128/jb.175.16.5117-5128.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Henry J. L., Jaikaran E. S., Davies J. R., Tomlinson A. J., Mason P. J., Barnes J. M., Beale A. J. A study of poliovaccination in infancy: excretion following challenge with live virus by children given killed or living poliovaccine. J Hyg (Lond) 1966 Mar;64(1):105–120. doi: 10.1017/s0022172400040389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
  31. Holmgren J., Czerkinsky C., Lycke N., Svennerholm A. M. Mucosal immunity: implications for vaccine development. Immunobiology. 1992 Feb;184(2-3):157–179. doi: 10.1016/S0171-2985(11)80473-0. [DOI] [PubMed] [Google Scholar]
  32. Hone D. M., Harris A. M., Chatfield S., Dougan G., Levine M. M. Construction of genetically defined double aro mutants of Salmonella typhi. Vaccine. 1991 Nov;9(11):810–816. doi: 10.1016/0264-410x(91)90218-u. [DOI] [PubMed] [Google Scholar]
  33. Iwata M., Sato A. Morphological and immunohistochemical studies of the lungs and bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa. Infect Immun. 1991 Apr;59(4):1514–1520. doi: 10.1128/iai.59.4.1514-1520.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Koch C., Høiby N. Pathogenesis of cystic fibrosis. Lancet. 1993 Apr 24;341(8852):1065–1069. doi: 10.1016/0140-6736(93)92422-p. [DOI] [PubMed] [Google Scholar]
  35. Koskinen S., Tölö H., Hirvonen M., Koistinen J. Long-term persistence of selective IgA deficiency in healthy adults. J Clin Immunol. 1994 Mar;14(2):116–119. doi: 10.1007/BF01541344. [DOI] [PubMed] [Google Scholar]
  36. LANCEFIELD R. C. Persistence of type-specific antibodies in man following infection with group A streptococci. J Exp Med. 1959 Aug 1;110(2):271–292. doi: 10.1084/jem.110.2.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. MARINE W. M., CHIN T. D., GRAVELLE C. R. Limitation of fecal and pharyngeal poliovirus excretion in Salk-vaccinated children. A family study during a type 1 poliomyelitis epidemic. Am J Hyg. 1962 Sep;76:173–195. doi: 10.1093/oxfordjournals.aje.a120272. [DOI] [PubMed] [Google Scholar]
  38. Michetti P., Mahan M. J., Slauch J. M., Mekalanos J. J., Neutra M. R. Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect Immun. 1992 May;60(5):1786–1792. doi: 10.1128/iai.60.5.1786-1792.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Miller S. I., Kukral A. M., Mekalanos J. J. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5054–5058. doi: 10.1073/pnas.86.13.5054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Morgan G., Levinsky R. J. Clinical significance of IgA deficiency. Arch Dis Child. 1988 Jun;63(6):579–581. doi: 10.1136/adc.63.6.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Moss R. B., Carmack M. A., Esrig S. Deficiency of IgG4 in children: association of isolated IgG4 deficiency with recurrent respiratory tract infection. J Pediatr. 1992 Jan;120(1):16–21. doi: 10.1016/s0022-3476(05)80590-6. [DOI] [PubMed] [Google Scholar]
  42. Ogra P. L. Global eradication of poliomyelitis: reinvent the wheel or use existing options effectively? Public Health Rev. 1993;21(1-2):143–150. [PubMed] [Google Scholar]
  43. Oishi K., Sonoda F., Iwagaki A., Ponglertnapagorn P., Watanabe K., Nagatake T., Siadak A., Pollack M., Matsumoto K. Therapeutic effects of a human antiflagella monoclonal antibody in a neutropenic murine model of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 1993 Feb;37(2):164–170. doi: 10.1128/aac.37.2.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pier G. B., Koles N. L., Meluleni G., Hatano K., Pollack M. Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06. Infect Immun. 1994 Apr;62(4):1137–1143. doi: 10.1128/iai.62.4.1137-1143.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pier G. B., Meluleni G., Neuger E. A murine model of chronic mucosal colonization by Pseudomonas aeruginosa. Infect Immun. 1992 Nov;60(11):4768–4776. doi: 10.1128/iai.60.11.4768-4776.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Pier G. B., Thomas D., Small G., Siadak A., Zweerink H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1989 Jan;57(1):174–179. doi: 10.1128/iai.57.1.174-179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Poggio E. C., Glynn R. J., Schein O. D., Seddon J. M., Shannon M. J., Scardino V. A., Kenyon K. R. The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med. 1989 Sep 21;321(12):779–783. doi: 10.1056/NEJM198909213211202. [DOI] [PubMed] [Google Scholar]
  48. Robbins J. B., Schneerson R. Polysaccharide-protein conjugates: a new generation of vaccines. J Infect Dis. 1990 May;161(5):821–832. doi: 10.1093/infdis/161.5.821. [DOI] [PubMed] [Google Scholar]
  49. Salk D. Eradication of poliomyelitis in the United States. II. Experience with killed poliovirus vaccine. Rev Infect Dis. 1980 Mar-Apr;2(2):243–257. doi: 10.1093/clinids/2.2.243. [DOI] [PubMed] [Google Scholar]
  50. Schaffer F. M., Monteiro R. C., Volanakis J. E., Cooper M. D. IgA deficiency. Immunodefic Rev. 1991;3(1):15–44. [PubMed] [Google Scholar]
  51. Schein O. D., Glynn R. J., Poggio E. C., Seddon J. M., Kenyon K. R. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med. 1989 Sep 21;321(12):773–778. doi: 10.1056/NEJM198909213211201. [DOI] [PubMed] [Google Scholar]
  52. Spinozzi F., Cimignoli E., Gerli R., Agea E., Bertotto A., Rondoni F., Grignani F. IgG subclass deficiency and sinopulmonary bacterial infections in patients with alcoholic liver disease. Arch Intern Med. 1992 Jan;152(1):99–104. [PubMed] [Google Scholar]
  53. Strober W., Sneller M. C. IgA deficiency. Ann Allergy. 1991 May;66(5):363–375. [PubMed] [Google Scholar]
  54. Toth A., Schödel F., Duchêne M., Massarrat K., Blum B., Schmitt A., Domdey H., von Specht B. U. Protection of immunosuppressed mice against translocation of Pseudomonas aeruginosa from the gut by oral immunization with recombinant Pseudomonas aeruginosa outer membrane protein I expressing Salmonella dublin. Vaccine. 1994 Oct;12(13):1215–1221. doi: 10.1016/0264-410x(94)90246-1. [DOI] [PubMed] [Google Scholar]
  55. Ugazio A. G., Out T. A., Plebani A., Duse M., Monafo V., Nespoli L., Burgio G. R. Recurrent infections in children with "selective" IgA deficiency: association with IgG2 and IgG4 deficiency. Birth Defects Orig Artic Ser. 1983;19(3):169–171. [PubMed] [Google Scholar]
  56. Umetsu D. T., Ambrosino D. M., Quinti I., Siber G. R., Geha R. S. Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. N Engl J Med. 1985 Nov 14;313(20):1247–1251. doi: 10.1056/NEJM198511143132002. [DOI] [PubMed] [Google Scholar]
  57. Wells C. L., Jechorek R. P., Gillingham K. J. Relative contributions of host and microbial factors in bacterial translocation. Arch Surg. 1991 Feb;126(2):247–252. doi: 10.1001/archsurg.1991.01410260137020. [DOI] [PubMed] [Google Scholar]
  58. Winner L., 3rd, Mack J., Weltzin R., Mekalanos J. J., Kraehenbuhl J. P., Neutra M. R. New model for analysis of mucosal immunity: intestinal secretion of specific monoclonal immunoglobulin A from hybridoma tumors protects against Vibrio cholerae infection. Infect Immun. 1991 Mar;59(3):977–982. doi: 10.1128/iai.59.3.977-982.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Xu H. R., Hsu H. S. Dissemination and proliferation of Salmonella typhimurium in genetically resistant and susceptible mice. J Med Microbiol. 1992 Jun;36(6):377–381. doi: 10.1099/00222615-36-6-377. [DOI] [PubMed] [Google Scholar]

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