Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide.

Author information

Affiliations

  • 1. Department of Microbiology, Kaplan Cancer Center, New York University Medical Center, New York 10016.
      Authors
    • Kamijo R 1
    (1 author)

ORCIDs linked to this article

The Journal of Experimental Medicine, 01 Oct 1993, 178(4):1435-1440
https://doi.org/10.1084/jem.178.4.1435 PMID: 8376946 PMCID: PMC2191201

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC

Abstract 

Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis. BCG infection was not lethal for wild-type mice whereas all IFN-gamma R0/0 mice died approximately 7-9 wk after inoculation. Histological examination at 2 and 6 wk after BCG inoculation showed that livers of IFN-gamma R0/0 mice had higher numbers of acid-fast bacteria than wild-type mice, especially at 6 wk. In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation. Injection of lipopolysaccharide (LPS) 2 wk after BCG inoculation was significantly less lethal for IFN-gamma R0/0 mice than for wild-type mice. Reduced lethality of LPS correlated with a drastically reduced production of tumor necrosis factor alpha (TNF-alpha) in the IFN-gamma R0/0 mice. Interleukin 1 alpha (IL-1 alpha) and IL-6 levels in the serum were also significantly reduced in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced capacity of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection. These results show that the presence of a functional IFN-gamma receptor is essential for the recovery of mice from BCG infection, and that IFN-gamma is a key element in the complex process whereby BCG infection leads to the sensitization to endotoxin.

Free full text 

Logo of jexpmedLink to Publisher's site
J Exp Med. 1993 Oct 1; 178(4): 1435–1440.
PMCID: PMC2191201
PMID: 8376946

Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent challenge with lipopolysaccharide

Copyright and License information Disclaimer

Abstract

Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis. BCG infection was not lethal for wild-type mice whereas all IFN-gamma R0/0 mice died approximately 7-9 wk after inoculation. Histological examination at 2 and 6 wk after BCG inoculation showed that livers of IFN-gamma R0/0 mice had higher numbers of acid-fast bacteria than wild- type mice, especially at 6 wk. In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation. Injection of lipopolysaccharide (LPS) 2 wk after BCG inoculation was significantly less lethal for IFN- gamma R0/0 mice than for wild-type mice. Reduced lethality of LPS correlated with a drastically reduced production of tumor necrosis factor alpha (TNF-alpha) in the IFN-gamma R0/0 mice. Interleukin 1 alpha (IL-1 alpha) and IL-6 levels in the serum were also significantly reduced in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced capacity of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection. These results show that the presence of a functional IFN-gamma receptor is essential for the recovery of mice from BCG infection, and that IFN-gamma is a key element in the complex process whereby BCG infection leads to the sensitization to endotoxin.

Full Text

The Full Text of this article is available as a PDF (1.0M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Blanden RV, Lefford MJ, Mackaness GB. The host response to Calmette-Guérin bacillus infection in mice. J Exp Med. 1969 May 1;129(5):1079–1107. [Europe PMC free article] [Abstract] [Google Scholar]
  • Flynn JL, Goldstein MM, Triebold KJ, Koller B, Bloom BR. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013–12017. [Europe PMC free article] [Abstract] [Google Scholar]
  • OLD LJ, CLARKE DA, BENACERRAF B. Effect of Bacillus Calmette-Guerin infection on transplanted tumours in the mouse. Nature. 1959 Jul 25;184(Suppl 5):291–292. [Abstract] [Google Scholar]
  • Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. [Europe PMC free article] [Abstract] [Google Scholar]
  • Youngner JS, Stinebring WR. Interferon appearance stimulated by endotoxin, bacteria, or viruses in mice pre-treated with Escherichia coli endotoxin or infected with Mycobacterium tuberculosis. Nature. 1965 Oct 30;208(5009):456–458. [Abstract] [Google Scholar]
  • Salvin SB, Ribi E, Granger DL, Youngner JS. Migration inhibitory factor and type II interferon in the circulation of mice sensitized with mycobacterial components. J Immunol. 1975 Jan;114(1 Pt 2):354–359. [Abstract] [Google Scholar]
  • Pelletier M, Forget A, Bourassa D, Gros P, Skamene E. Immunopathology of BCG infection in genetically resistant and susceptible mouse strains. J Immunol. 1982 Nov;129(5):2179–2185. [Abstract] [Google Scholar]
  • Vidal SM, Malo D, Vogan K, Skamene E, Gros P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell. 1993 May 7;73(3):469–485. [Abstract] [Google Scholar]
  • Izzo AA, North RJ. Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells. J Exp Med. 1992 Aug 1;176(2):581–586. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. [Abstract] [Google Scholar]
  • Bermudez LE, Stevens P, Kolonoski P, Wu M, Young LS. Treatment of experimental disseminated Mycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor. J Immunol. 1989 Nov 1;143(9):2996–3000. [Abstract] [Google Scholar]
  • Denis M. Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis. J Leukoc Biol. 1991 Nov;50(5):495–501. [Abstract] [Google Scholar]
  • Banerjee DK, Sharp AK, Lowrie DB. The effect of gamma-interferon during Mycobacterium bovis (BCG) infection in athymic and euthymic mice. Microb Pathog. 1986 Apr;1(2):221–224. [Abstract] [Google Scholar]
  • Bermudez LE, Young LS. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol. 1988 May 1;140(9):3006–3013. [Abstract] [Google Scholar]
  • Douvas GS, Looker DL, Vatter AE, Crowle AJ. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect Immun. 1985 Oct;50(1):1–8. [Europe PMC free article] [Abstract] [Google Scholar]
  • Squires KE, Murphy WF, Madoff LC, Murray HW. Interferon-gamma and Mycobacterium avium-intracellulare infection. J Infect Dis. 1989 Mar;159(3):599–600. [Abstract] [Google Scholar]
  • Shiratsuchi H, Johnson JL, Ellner JJ. Bidirectional effects of cytokines on the growth of Mycobacterium avium within human monocytes. J Immunol. 1991 May 1;146(9):3165–3170. [Abstract] [Google Scholar]
  • Chan J, Xing Y, Magliozzo RS, Bloom BR. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med. 1992 Apr 1;175(4):1111–1122. [Europe PMC free article] [Abstract] [Google Scholar]
  • Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742–1745. [Abstract] [Google Scholar]
  • Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. [Abstract] [Google Scholar]
  • Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. [Abstract] [Google Scholar]
  • Beutler B, Tkacenko V, Milsark I, Krochin N, Cerami A. Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. J Exp Med. 1986 Nov 1;164(5):1791–1796. [Europe PMC free article] [Abstract] [Google Scholar]
  • Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [Abstract] [Google Scholar]
  • Kamijo R, Shapiro D, Le J, Huang S, Aguet M, Vilcek J. Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6626–6630. [Europe PMC free article] [Abstract] [Google Scholar]
  • Heremans H, Van Damme J, Dillen C, Dijkmans R, Billiau A. Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice. J Exp Med. 1990 Jun 1;171(6):1853–1869. [Europe PMC free article] [Abstract] [Google Scholar]
  • Grau GE, Fajardo LF, Piguet PF, Allet B, Lambert PH, Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. [Abstract] [Google Scholar]
  • Grau GE, Heremans H, Piguet PF, Pointaire P, Lambert PH, Billiau A, Vassalli P. Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5572–5574. [Europe PMC free article] [Abstract] [Google Scholar]
Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Full text links 

Read article at publisher's site: https://doi.org/10.1084/jem.178.4.1435

Read article for free, from open access legal sources, via Unpaywall: https://rupress.org/jem/article-pdf/178/4/1435/1104280/1435.pdfUnpaywall

Citations & impact 

Impact metrics

228
Citations
Jump to Citations
6
Data citations
Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/20979645
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/20979645

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1084/jem.178.4.1435

Supporting
Mentioning
Contrasting
20
197
1

Article citations

Go to all (228) article citations

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

NCI NIH HHS (2)

NIAID NIH HHS (1)