• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. Dec 1, 1993; 178(6): 2249–2254.
PMCID: PMC2191274

An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection

Abstract

Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell- mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.

Full Text

The Full Text of this article is available as a PDF (649K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Belosevic M, Davis CE, Meltzer MS, Nacy CA. Regulation of activated macrophage antimicrobial activities. Identification of lymphokines that cooperate with IFN-gamma for induction of resistance to infection. J Immunol. 1988 Aug 1;141(3):890–896. [PubMed]
  • Liew FY, Millott S, Parkinson C, Palmer RM, Moncada S. Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol. 1990 Jun 15;144(12):4794–4797. [PubMed]
  • Murray HW, Rubin BY, Rothermel CD. 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. [PMC free article] [PubMed]
  • Kiderlen AF, Kaufmann SH, Lohmann-Matthes ML. Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant immune interferon. Eur J Immunol. 1984 Oct;14(10):964–967. [PubMed]
  • Sasaki T, Mieno M, Udono H, Yamaguchi K, Usui T, Hara K, Shiku H, Nakayama E. Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection. J Exp Med. 1990 Apr 1;171(4):1141–1154. [PMC free article] [PubMed]
  • Buchmeier NA, Schreiber RD. Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7404–7408. [PMC free article] [PubMed]
  • Barnes PF, Fong SJ, Brennan PJ, Twomey PE, Mazumder A, Modlin RL. Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis. J Immunol. 1990 Jul 1;145(1):149–154. [PubMed]
  • Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. [PubMed]
  • Nathan CF, Kaplan G, Levis WR, Nusrat A, Witmer MD, Sherwin SA, Job CK, Horowitz CR, Steinman RM, Cohn ZA. Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy. N Engl J Med. 1986 Jul 3;315(1):6–15. [PubMed]
  • Kaplan G, Nusrat A, Sarno EN, Job CK, McElrath J, Porto JA, Nathan CF, Cohn ZA. Cellular responses to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients. Am J Pathol. 1987 Aug;128(2):345–353. [PMC free article] [PubMed]
  • Orme IM, Miller ES, Roberts AD, Furney SK, Griffin JP, Dobos KM, Chi D, Rivoire B, Brennan PJ. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J Immunol. 1992 Jan 1;148(1):189–196. [PubMed]
  • 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. [PubMed]
  • Granger DL, Hibbs JB, Jr, Broadnax LM. Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine. J Immunol. 1991 Feb 15;146(4):1294–1302. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Xie QW, Cho HJ, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Ding A, Troso T, Nathan C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992 Apr 10;256(5054):225–228. [PubMed]
  • Denis M. Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis. J Leukoc Biol. 1991 Nov;50(5):495–501. [PubMed]
  • Denis M. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol. 1991 Jan;132(1):150–157. [PubMed]
  • Stuehr DJ, Marletta MA. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7738–7742. [PMC free article] [PubMed]
  • Lyons CR, Orloff GJ, Cunningham JM. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992 Mar 25;267(9):6370–6374. [PubMed]
  • Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711–6715. [PMC free article] [PubMed]
  • Murray HW, Rubin BY, Masur H, Roberts RB. Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med. 1984 Apr 5;310(14):883–889. [PubMed]
  • Clerici M, Shearer GM. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993 Mar;14(3):107–111. [PubMed]
  • Hill AR, Premkumar S, Brustein S, Vaidya K, Powell S, Li PW, Suster B. Disseminated tuberculosis in the acquired immunodeficiency syndrome era. Am Rev Respir Dis. 1991 Nov;144(5):1164–1170. [PubMed]
  • Abouya YL, Beaumel A, Lucas S, Dago-Akribi A, Coulibaly G, N'Dhatz M, Konan JB, Yapi A, De Cock KM. Pneumocystis carinii pneumonia. An uncommon cause of death in African patients with acquired immunodeficiency syndrome. Am Rev Respir Dis. 1992 Mar;145(3):617–620. [PubMed]
  • Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993 Dec 1;178(6):2243–2247. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...