Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1992 May;60(5):2115–2120. doi: 10.1128/iai.60.5.2115-2120.1992

Inhibition of expression of major histocompatibility complex class II molecules in macrophages infected with Leishmania donovani occurs at the level of gene transcription via a cyclic AMP-independent mechanism.

W C Kwan 1, W R McMaster 1, N Wong 1, N E Reiner 1
PMCID: PMC257124  PMID: 1314226

Abstract

Among the important pleiotropic responses to gamma interferon (IFN-gamma) during the activation of macrophages (M phi) is the increased expression of major histocompatibility complex class II genes. In the present study, infection with Leishmania donovani was shown to inhibit in parallel the induction by IFN-gamma of H-2 A beta gene transcription, class II mRNA accumulation, and H-2 Ad protein expression in cells of the murine macrophage cell line P388D1. Treatment of P388D1 cells with either the adenylate cyclase activator cholera toxin or the protein kinase A activator N6-2'-O-dibutyryl cyclic AMP (dibutyryl cAMP) similarly inhibited the induction by IFN-gamma of class II protein expression, and in parallel with Leishmania infection, cholera toxin inhibited the induction of mRNA for the H-2 A alpha and H-2 A beta proteins. Concentrations of intracellular cAMP were significantly increased in cholera toxin-treated cells but not in leishmania-infected cells. These findings indicate that at least one mechanism by which Leishmania infection attenuates the activation of M phi by IFN-gamma involves selective, transcriptional inhibition of major histocompatibility complex class II genes via a cAMP-independent mechanism.

Full text

PDF
2120

Images in this article

Selected References

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

  1. Amaldi I., Reith W., Berte C., Mach B. Induction of HLA class II genes by IFN-gamma is transcriptional and requires a trans-acting protein. J Immunol. 1989 Feb 1;142(3):999–1004. [PubMed] [Google Scholar]
  2. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. Regions of allelic hypervariability in the murine A alpha immune response gene. Cell. 1983 Aug;34(1):169–177. doi: 10.1016/0092-8674(83)90147-2. [DOI] [PubMed] [Google Scholar]
  3. Blanar M. A., Boettger E. C., Flavell R. A. Transcriptional activation of HLA-DR alpha by interferon gamma requires a trans-acting protein. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4672–4676. doi: 10.1073/pnas.85.13.4672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cailla H. L., Racine-Weisbuch M. S., Delaage M. A. Adenosine 3',5' cyclic monophosphate assay at 10-15 mole level. Anal Biochem. 1973 Dec;56(2):394–407. doi: 10.1016/0003-2697(73)90205-4. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Degen J. L., Neubauer M. G., Degen S. J., Seyfried C. E., Morris D. R. Regulation of protein synthesis in mitogen-activated bovine lymphocytes. Analysis of actin-specific and total mRNA accumulation and utilization. J Biol Chem. 1983 Oct 25;258(20):12153–12162. [PubMed] [Google Scholar]
  7. Didier D. K., Schiffenbauer J., Woulfe S. L., Zacheis M., Schwartz B. D. Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7322–7326. doi: 10.1073/pnas.85.19.7322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Figueíredo F., Uhing R. J., Okonogi K., Gettys T. W., Johnson S. P., Adams D. O., Prpic V. Activation of the cAMP cascade inhibits an early event involved in murine macrophage Ia expression. J Biol Chem. 1990 Jul 25;265(21):12317–12323. [PubMed] [Google Scholar]
  9. Kaye P. M., Sims M., Feldmann M. Regulation of macrophage accessory cell activity by mycobacteria. II. In vitro inhibition of Ia expression by Mycobacterium microti. Clin Exp Immunol. 1986 Apr;64(1):28–34. [PMC free article] [PubMed] [Google Scholar]
  10. Liou H. C., Boothby M. R., Finn P. W., Davidon R., Nabavi N., Zeleznik-Le N. J., Ting J. P., Glimcher L. H. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 1990 Mar 30;247(4950):1581–1584. doi: 10.1126/science.2321018. [DOI] [PubMed] [Google Scholar]
  11. Liou H. C., Boothby M. R., Glimcher L. H. Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Science. 1988 Oct 7;242(4875):69–71. doi: 10.1126/science.3140376. [DOI] [PubMed] [Google Scholar]
  12. Reiner N. E., Malemud C. J. Arachidonic acid metabolism by murine peritoneal macrophages infected with Leishmania donovani: in vitro evidence for parasite-induced alterations in cyclooxygenase and lipoxygenase pathways. J Immunol. 1985 Jan;134(1):556–563. [PubMed] [Google Scholar]
  13. Reiner N. E., Ng W., Ma T., McMaster W. R. Kinetics of gamma interferon binding and induction of major histocompatibility complex class II mRNA in Leishmania-infected macrophages. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4330–4334. doi: 10.1073/pnas.85.12.4330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reiner N. E., Ng W., McMaster W. R. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J Immunol. 1987 Mar 15;138(6):1926–1932. [PubMed] [Google Scholar]
  15. Robinson R. R., Germain R. N., McKean D. J., Mescher M., Seidman J. G. Extensive polymorphism surrounding the murine Ia A beta chain gene. J Immunol. 1983 Oct;131(4):2025–2031. [PubMed] [Google Scholar]
  16. Snyder D. S., Beller D. I., Unanue E. R. Prostaglandins modulate macrophage Ia expression. Nature. 1982 Sep 9;299(5879):163–165. doi: 10.1038/299163a0. [DOI] [PubMed] [Google Scholar]
  17. Steeg P. S., Johnson H. M., Oppenheim J. J. Regulation of murine macrophage Ia antigen expression by an immune interferon-like lymphokine: inhibitory effect of endotoxin. J Immunol. 1982 Dec;129(6):2402–2406. [PubMed] [Google Scholar]
  18. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  19. Virgin H. W., 4th, Wittenberg G. F., Unanue E. R. Immune complex effects on murine macrophages. I. Immune complexes suppress interferon-gamma induction of Ia expression. J Immunol. 1985 Dec;135(6):3735–3743. [PubMed] [Google Scholar]

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

RESOURCES