Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jul;75(7):3395–3399. doi: 10.1073/pnas.75.7.3395

Enhancement of the neonate's nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant.

M Parant, F Parant, L Chedid
PMCID: PMC392783  PMID: 356054

Abstract

N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) and certain derivatives that are structural analogs of part of the bacterial peptidoglycan monomer have been shown to be adjuvant active and to enhance the nonspecific immunity of adult mice infected by Klebsiella pneumoniae. In the present study muramyl dipeptide and two other synthetic analogs were found to be active in newborn mice. This activity could be demonstrated after administration by subcutaneous or even by oral route. In contrast to what was observed after treatment by lipopolysaccharide, 8-day-old mice were definitively protected against bacterial challenge by these glycopeptides. Therefore such molecules could have a great value in view of studying and correcting the neonate's unresponsiveness.

Full text

PDF
3395

Selected References

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

  1. Argyris B. F. Role of macrophages in immunological maturation. J Exp Med. 1968 Sep 1;128(3):459–467. doi: 10.1084/jem.128.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BILLINGHAM R. E., BRENT L. Acquired tolerance of foreign cells in newborn animals. Proc R Soc Lond B Biol Sci. 1956 Nov 13;146(922):78–90. doi: 10.1098/rspb.1956.0073. [DOI] [PubMed] [Google Scholar]
  3. BIOZZI G., BENACERRAF B., HALPERN B. N. Quantitative study of the granulopectic activity of the reticulo-endothelial system. II. A study of the kinetics of the R. E. S. in relation to the dose of carbon injected; relationship between the weight of the organs and their activity. Br J Exp Pathol. 1953 Aug;34(4):441–457. [PMC free article] [PubMed] [Google Scholar]
  4. BIOZZI G., BENACERRAF B., HALPERN B. N. The effect of Salm. typhi and its endotoxin on the phagocytic activity of the reticuloendothelial system in mice. Br J Exp Pathol. 1955 Jun;36(3):226–235. [PMC free article] [PubMed] [Google Scholar]
  5. Blanden R. V., Lefford M. J., Mackaness G. B. The host response to Calmette-Guérin bacillus infection in mice. J Exp Med. 1969 May 1;129(5):1079–1107. doi: 10.1084/jem.129.5.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHEDID L., PARANT M. [Study of the tolerance of adrenalectomized mice using an endotoxin labeled with Cr-51]. Ann Inst Pasteur (Paris) 1961 Aug;101:170–177. [PubMed] [Google Scholar]
  7. Calkins C. E., Stutman O. Changes in suppressor mechanisms during postnatal development in mice. J Exp Med. 1978 Jan 1;147(1):87–97. doi: 10.1084/jem.147.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chedid L., Audibert F., Lefrancier P., Choay J., Lederer E. Modulation of the immune response by a synthetic adjuvant and analogs. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2472–2475. doi: 10.1073/pnas.73.7.2472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chedid L., Parant M., Damais C., Parant F., Juy D., Galelli A. Failure of endotoxin to increase nonspecific resistance to infection of lipopolysaccharide low-responder mice. Infect Immun. 1976 Mar;13(3):722–727. doi: 10.1128/iai.13.3.722-727.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chedid L., Parant M., Parant F., Boyer F. A proposed mechanism for natural immunity to enterobacterial pathogens. J Immunol. 1968 Feb;100(2):292–306. [PubMed] [Google Scholar]
  11. Chedid L., Parant M., Parant F., Lefrancher P., Choay J., Lederer E. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. Proc Natl Acad Sci U S A. 1977 May;74(5):2089–2093. doi: 10.1073/pnas.74.5.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DUBOS R. J., SCHAEDLER R. W. Effects of cellular constituents of mycobacteria on the resistance of mice to heterologous infections I. Protective effects. J Exp Med. 1957 Nov 1;106(5):703–717. doi: 10.1084/jem.106.5.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DUBOS R. J., SCHAEDLER R. W. Reversible changes in the susceptibility of mice to bacterial infections. I. Changes brought about by injection of pertussis vaccine or of bacterial endotoxins. J Exp Med. 1956 Jul 1;104(1):53–65. doi: 10.1084/jem.104.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Elin R. J., Wolff S. M. Nonspecificity of the limulus amebocyte lysate test: positive reactions with polynucleotides and proteins. J Infect Dis. 1973 Sep;128(3):349–352. doi: 10.1093/infdis/128.3.349. [DOI] [PubMed] [Google Scholar]
  15. Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
  16. HOWARD J. G., BIOZZI G., HALPERN B. N., STIFFEL C., MOUTON D. The effect of Mycobacterium tuberculosis (BCG) infection on the resistance of mice to bacterial endotoxin and Salmonella enteritidis infection. Br J Exp Pathol. 1959 Jun;40(3):281–290. [PMC free article] [PubMed] [Google Scholar]
  17. Hardy B., Mozes E., Danon D. Comparison of the immune response potential of newborn mice to T-dependent and T-independent synthetic polypeptides. Immunology. 1976 Feb;30(2):261–266. [PMC free article] [PubMed] [Google Scholar]
  18. JOHNSON A. G., GAINES S., LANDY M. Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. J Exp Med. 1956 Feb 1;103(2):225–246. doi: 10.1084/jem.103.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Juy D., Chedid L. Comparison between macrophage activation and enhancement of nonspecific resistance to tumors by mycobacterial immunoadjuvants. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4105–4109. doi: 10.1073/pnas.72.10.4105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kotani S., Watanabe Y., Kinoshita F., Kato K., Harada K. Gelation of the amoebocyte lysate of Tachypleus tridentatus by cell wall digest of several gram-positive bacteria and synthetic peptidoglycan subunits of natural and unnatural configurations. Biken J. 1977 Mar;20(1):5–10. [PubMed] [Google Scholar]
  21. Kotani S., Watanabe Y., Shimono T., Harada K., Shiba T. Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids. Biken J. 1976 Mar;19(1):9–13. [PubMed] [Google Scholar]
  22. Lefrancier P., Choay J., Derrien M., Lederman I. Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response, and of some n-acetyl-muramyl-peptide analogs. Int J Pept Protein Res. 1977;9(4):249–257. doi: 10.1111/j.1399-3011.1977.tb03488.x. [DOI] [PubMed] [Google Scholar]
  23. Löwy I., Bona C., Chedid L. Target cells for the activity of a synthetic adjuvant: muramyl dipeptide. Cell Immunol. 1977 Mar 1;29(1):195–199. doi: 10.1016/0008-8749(77)90288-x. [DOI] [PubMed] [Google Scholar]
  24. Mosier D. E., Johnson B. M. Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes. J Exp Med. 1975 Jan 1;141(1):216–226. doi: 10.1084/jem.141.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mosier D. E., Zaldivar N. M., Goldings E., Mond J., Scher I., Paul W. E. Formation of antibody in the newborn mouse: study of T-cell-independent antibody response. J Infect Dis. 1977 Aug;136 (Suppl):S14–S19. doi: 10.1093/infdis/136.supplement.s14. [DOI] [PubMed] [Google Scholar]
  26. PARANT M., BOYER F., CHEDID L. AUGMENTATION DE LA R'ESISTANCE AUX INFECTIONS CONS'ECUTIVE 'A UNE INJECTION D'ENDOTOXINE. MISE EN 'EVIDENCE DU M'ECANISME PAR L'ASSOCIATION DE SULFAMIDE. C R Hebd Seances Acad Sci. 1965 Mar 1;260:2630–2633. [PubMed] [Google Scholar]
  27. Parant M., Galelli A., Parant F., Chedid L. Role of B-lymphocytes in nonspecific resistance to Klebsiella pneumoniae infection of endotoxin-treated mice. J Infect Dis. 1976 Dec;134(6):531–539. doi: 10.1093/infdis/134.6.531. [DOI] [PubMed] [Google Scholar]
  28. Parant M., Sacquet E. Augmentation de la résistance à l'infection du souriceau conventionnel ou oxénique après une injection d'endotoxine. C R Acad Sci Hebd Seances Acad Sci D. 1966 Apr 25;262(17):1914–1917. [PubMed] [Google Scholar]
  29. Rudbach J. A., Akiya F. I., Elin R. J., Hochstein H. D., Luoma M. K., Milner E. C., Milner K. C., Thomas K. R. Preparation and properties of a national reference endotoxin. J Clin Microbiol. 1976 Jan;3(1):21–25. doi: 10.1128/jcm.3.1.21-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sherr D. H., Szewczuk M. R., Siskind G. W. Ontogeny of B-lymphocyte function. V. Thymus cell involvement in the functional maturation of B-lymphocytes from fetal mice transferred into adult irradiated hosts. J Exp Med. 1978 Jan 1;147(1):196–206. doi: 10.1084/jem.147.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spear P. G., Edelman G. M. Maturation of the humoral immune response in mice. J Exp Med. 1974 Feb 1;139(2):249–263. doi: 10.1084/jem.139.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sugimoto M., Germain R. N., Chedid L., Benacerraf B. Enhancement of carrier-specific helper T cell function by the synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP). J Immunol. 1978 Mar;120(3):980–982. [PubMed] [Google Scholar]
  33. Tanaka A., Nagao S., Saito R., Kotani S., Kusumoto S., Shiba T. Correlation of stereochemically specific structure in muramyl dipeptide between macrophage activation and adjuvant activity. Biochem Biophys Res Commun. 1977 Jul 25;77(2):621–627. doi: 10.1016/s0006-291x(77)80024-7. [DOI] [PubMed] [Google Scholar]
  34. WEISS D. W., BONHAG R. S., PARKS J. A. STUDIES ON THE HETEROLOGOUS IMMUNOGENICITY OF A MENTHANOL-INSOLUBLE FRACTION OF ATTENUATED TUBERCLE BACILLI (BCG). I. ANTIMICROBIAL PROTECTION. J Exp Med. 1964 Jan 1;119:53–70. doi: 10.1084/jem.119.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES