Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 May;63(5):1870–1875. doi: 10.1128/iai.63.5.1870-1875.1995

Potentiation of interferon-mediated inhibition of Chlamydia infection by interleukin-1 in human macrophage cultures.

J M Carlin 1, J B Weller 1
PMCID: PMC173237  PMID: 7537250

Abstract

One mechanism by which interferons (IFNs) can inhibit chlamydial infection is by the induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which restricts the availability of tryptophan, which is required for chlamydial growth. Other immunomodulating agents, including interleukin-1 (IL-1), can interact synergistically with IFNs, resulting in increased IDO activity in macrophages. The objectives of this study were to establish that IL-1 can enhance IFN-mediated inhibition of chlamydial growth by increasing the amount of IDO activity induced by IFNs and to identify immunomodulatory agents in culture supernatants from chlamydia-infected macrophages that interact synergistically with IFNs in restricting chlamydial growth. Monocyte-derived macrophages were treated with IL-1 combined with gamma IFN (IFN-gamma) or IFN-beta. The ability of treated cells to support the growth of Chlamydia psittaci was directly related to the amount of IDO activity induced; as IDO activity increased, so did inhibition of chlamydial growth. Furthermore, concentrations of IFNs were identified at which little IDO activity was induced and chlamydial growth was permitted yet which in the presence of IL-1 resulted in increased IDO activity and restriction of chlamydial growth. The addition of exogenous tryptophan reversed the effect of combined IFN and IL-1 treatment, indicating that IDO activity induced by combined cytokine treatment was responsible for chlamydial inhibition. Supernatants from chlamydia-infected macrophages were capable of potentiating IDO induction by IFN-gamma and of restricting the growth of C. psittaci. Antibody to IL-1 beta neutralized the potentiating effects of supernatants from chlamydia-infected cells on both IDO induction and chlamydial inhibition. Thus, IL-1 produced in response to chlamydial infection may contribute to the elimination of the infection.

Full Text

The Full Text of this article is available as a PDF (250.7 KB).

Selected References

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

  1. Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
  2. Beatty W. L., Belanger T. A., Desai A. A., Morrison R. P., Byrne G. I. Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Infect Immun. 1994 Sep;62(9):3705–3711. doi: 10.1128/iai.62.9.3705-3711.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998–4002. doi: 10.1073/pnas.90.9.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Byrne G. I., Faubion C. L. Lymphokine-mediated microbistatic mechanisms restrict Chlamydia psittaci growth in macrophages. J Immunol. 1982 Jan;128(1):469–474. [PubMed] [Google Scholar]
  5. Byrne G. I., Lehmann L. K., Landry G. J. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun. 1986 Aug;53(2):347–351. doi: 10.1128/iai.53.2.347-351.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Byrne G. I., Moulder J. W. Parasite-specified phagocytosis of Chlamydia psittaci and Chlamydia trachomatis by L and HeLa cells. Infect Immun. 1978 Feb;19(2):598–606. doi: 10.1128/iai.19.2.598-606.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Byrne G. I. Requirements for ingestion of Chlamydia psittaci by mouse fibroblasts (L cells). Infect Immun. 1976 Sep;14(3):645–651. doi: 10.1128/iai.14.3.645-651.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Caldwell H. D., Hitchcock P. J. Monoclonal antibody against a genus-specific antigen of Chlamydia species: location of the epitope on chlamydial lipopolysaccharide. Infect Immun. 1984 May;44(2):306–314. doi: 10.1128/iai.44.2.306-314.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carlin J. M., Borden E. C., Byrne G. I. Interferon-induced indoleamine 2,3-dioxygenase activity inhibits Chlamydia psittaci replication in human macrophages. J Interferon Res. 1989 Jun;9(3):329–337. doi: 10.1089/jir.1989.9.329. [DOI] [PubMed] [Google Scholar]
  10. Carlin J. M., Borden E. C., Sondel P. M., Byrne G. I. Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol. 1987 Oct 1;139(7):2414–2418. [PubMed] [Google Scholar]
  11. Carlin J. M., Borden E. C., Sondel P. M., Byrne G. I. Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J Leukoc Biol. 1989 Jan;45(1):29–34. doi: 10.1002/jlb.45.1.29. [DOI] [PubMed] [Google Scholar]
  12. Dayer J. M., de Rochemonteix B., Burrus B., Demczuk S., Dinarello C. A. Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest. 1986 Feb;77(2):645–648. doi: 10.1172/JCI112350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Green S. J., Meltzer M. S., Hibbs J. B., Jr, Nacy C. A. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990 Jan 1;144(1):278–283. [PubMed] [Google Scholar]
  14. Green S. J., Nacy C. A., Schreiber R. D., Granger D. L., Crawford R. M., Meltzer M. S., Fortier A. H. Neutralization of gamma interferon and tumor necrosis factor alpha blocks in vivo synthesis of nitrogen oxides from L-arginine and protection against Francisella tularensis infection in Mycobacterium bovis BCG-treated mice. Infect Immun. 1993 Feb;61(2):689–698. doi: 10.1128/iai.61.2.689-698.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hatch T. P. Competition between Chlamydia psittaci and L cells for host isoleucine pools: a limiting factor in chlamydial multiplication. Infect Immun. 1975 Jul;12(1):211–220. doi: 10.1128/iai.12.1.211-220.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hissong B. D., Byrne G. I., Padilla M. L., Carlin J. M. Upregulation of interferon-induced indoleamine 2,3-dioxygenase in human macrophage cultures by lipopolysaccharide, muramyl tripeptide, and interleukin-1. Cell Immunol. 1995 Feb;160(2):264–269. doi: 10.1016/0008-8749(95)80037-j. [DOI] [PubMed] [Google Scholar]
  17. Jiang X., Baldwin C. L. Effects of cytokines on intracellular growth of Brucella abortus. Infect Immun. 1993 Jan;61(1):124–134. doi: 10.1128/iai.61.1.124-134.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Magee D. M., Smith J. G., Bleicker C. A., Carter C. J., Bonewald L. F., Schachter J., Williams D. M. Chlamydia trachomatis pneumonia induces in vivo production of interleukin-1 and -6. Infect Immun. 1992 Mar;60(3):1217–1220. doi: 10.1128/iai.60.3.1217-1220.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meyer K. C., Cornwell R., Carlin J. M., Powers C., Irizarry A., Byrne G. I., Borden E. C. Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. Am J Respir Cell Mol Biol. 1992 Jun;6(6):639–646. doi: 10.1165/ajrcmb/6.6.639. [DOI] [PubMed] [Google Scholar]
  20. Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983 Oct;72(4):1506–1510. doi: 10.1172/JCI111107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Musso T., Gusella G. L., Brooks A., Longo D. L., Varesio L. Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes. Blood. 1994 Mar 1;83(5):1408–1411. [PubMed] [Google Scholar]
  22. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oswald I. P., Gazzinelli R. T., Sher A., James S. L. IL-10 synergizes with IL-4 and transforming growth factor-beta to inhibit macrophage cytotoxic activity. J Immunol. 1992 Jun 1;148(11):3578–3582. [PubMed] [Google Scholar]
  24. Paguirigan A. M., Byrne G. I., Becht S., Carlin J. M. Cytokine-mediated indoleamine 2,3-dioxygenase induction in response to Chlamydia infection in human macrophage cultures. Infect Immun. 1994 Apr;62(4):1131–1136. doi: 10.1128/iai.62.4.1131-1136.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pfefferkorn E. R., Guyre P. M. Inhibition of growth of Toxoplasma gondii in cultured fibroblasts by human recombinant gamma interferon. Infect Immun. 1984 May;44(2):211–216. doi: 10.1128/iai.44.2.211-216.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rothermel C. D., Rubin B. Y., Murray H. W. Gamma-interferon is the factor in lymphokine that activates human macrophages to inhibit intracellular Chlamydia psittaci replication. J Immunol. 1983 Nov;131(5):2542–2544. [PubMed] [Google Scholar]
  27. Rothermel C. D., Schachter J., Lavrich P., Lipsitz E. C., Francus T. Chlamydia trachomatis-induced production of interleukin-1 by human monocytes. Infect Immun. 1989 Sep;57(9):2705–2711. doi: 10.1128/iai.57.9.2705-2711.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schmidt J. A., Mizel S. B., Cohen D., Green I. Interleukin 1, a potential regulator of fibroblast proliferation. J Immunol. 1982 May;128(5):2177–2182. [PubMed] [Google Scholar]
  29. Schmitz J. L., Carlin J. M., Borden E. C., Byrne G. I. Beta interferon inhibits Toxoplasma gondii growth in human monocyte-derived macrophages. Infect Immun. 1989 Oct;57(10):3254–3256. doi: 10.1128/iai.57.10.3254-3256.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shemer Y., Sarov I. Inhibition of growth of Chlamydia trachomatis by human gamma interferon. Infect Immun. 1985 May;48(2):592–596. doi: 10.1128/iai.48.2.592-596.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shimizu T., Nomiyama S., Hirata F., Hayaishi O. Indoleamine 2,3-dioxygenase. Purification and some properties. J Biol Chem. 1978 Jul 10;253(13):4700–4706. [PubMed] [Google Scholar]
  32. Spielvogel R. L., Kersey J. H., Goltz R. W. Mononuclear cell stimulation of fibroblast collagen synthesis. Clin Exp Dermatol. 1978 Mar;3(1):25–30. doi: 10.1111/j.1365-2230.1978.tb01454.x. [DOI] [PubMed] [Google Scholar]
  33. Turco J., Winkler H. H. Cloned mouse interferon-gamma inhibits the growth of Rickettsia prowazekii in cultured mouse fibroblasts. J Exp Med. 1983 Dec 1;158(6):2159–2164. doi: 10.1084/jem.158.6.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yong S., Lau S. Rapid separation of tryptophan, kynurenines, and indoles using reversed-phase high-performance liquid chromatography. J Chromatogr. 1979 Jul 13;175(2):343–346. doi: 10.1016/s0021-9673(00)89443-1. [DOI] [PubMed] [Google Scholar]

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

RESOURCES