| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 147, Issue 7 2340-2345, Copyright © 1991 by American Association of Immunologists
ARTICLES |
LD Sibley, LB Adams, Y Fukutomi and JL Krahenbuhl
Immunology Department, G. W. L. Hansen's Disease Center, Carville, LA 70721.
IFN-gamma is an important mediator of cellular resistance against microbial pathogens and tumor cells due in part to its potent capacity to activate macrophages for enhanced cytotoxicity. The present study demonstrates that TNF-alpha regulates the expression of enhanced antimicrobial activity by triggering IFN-gamma primed macrophages to kill or inhibit intracellular Toxoplasma gondii. Resident mouse macrophages stimulated with rIFN-gamma at levels up to 2500 U/ml failed to display enhanced antitoxoplasmal activity when cultured in vitro under low endotoxin conditions (less than 10 pg/ml), but were triggered by addition of small amounts of LPS (0.1 ng/ml). A similar requirement for LPS as a second signal necessary to trigger antitoxoplasmal activity was observed when IFN-gamma was administered to mice in vivo. The essential nature of this triggering step allowed us to explore the role of cytokines that act as endogenous regulators of macrophage activation. rTNF-alpha, although unable to confer antitoxoplasmal activity when used alone to treat macrophages, was capable of triggering IFN-gamma-primed macrophages cultured under low endotoxin conditions. The ability of TNF-alpha to trigger IFN-gamma-primed macrophages was blocked by rabbit anti-TNF-alpha polyclonal antisera but was not affected by polymyxin B indicating that TNF-alpha triggering was not due to contamination with LPS. Collectively, these findings demonstrate that TNF-alpha performs an important regulatory role in the expression of enhanced anti-microbial activity by IFN-gamma- primed macrophages.
This article has been cited by other articles:
|
|
 |
|
  R. M. Andrade, M. Wessendarp, J.-A. C. Portillo, J.-Q. Yang, F. J. Gomez, J. E. Durbin, G. A. Bishop, and C. S. Subauste TNF Receptor-Associated Factor 6-Dependent CD40 Signaling Primes Macrophages to Acquire Antimicrobial Activity in Response to TNF-{alpha} J. Immunol., November 1, 2005; 175(9): 6014 - 6021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Andrade, M. Wessendarp, and C. S. Subauste CD154 Activates Macrophage Antimicrobial Activity in the Absence of IFN-{gamma} through a TNF-{alpha}-Dependent Mechanism J. Immunol., December 15, 2003; 171(12): 6750 - 6756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Mordue and L. D. Sibley A novel population of Gr-1+-activated macrophages induced during acute toxoplasmosis J. Leukoc. Biol., December 1, 2003; 74(6): 1015 - 1025. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Dobbin, N. C. Smith, and A. M. Johnson Heat Shock Protein 70 Is a Potential Virulence Factor in Murine Toxoplasma Infection Via Immunomodulation of Host NF-{kappa}B and Nitric Oxide J. Immunol., July 15, 2002; 169(2): 958 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Johnson and P. C. Sayles Deficient Humoral Responses Underlie Susceptibility to Toxoplasma gondii in CD4-Deficient Mice Infect. Immun., January 1, 2002; 70(1): 185 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Butcher, L. Kim, P. F. Johnson, and E. Y. Denkers Toxoplasma gondii Tachyzoites Inhibit Proinflammatory Cytokine Induction in Infected Macrophages by Preventing Nuclear Translocation of the Transcription Factor NF-{kappa}B J. Immunol., August 15, 2001; 167(4): 2193 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Das, N. Datta, S. Bandyopadhyay, and P. K. Das Successful Therapy of Lethal Murine Visceral Leishmaniasis with Cystatin Involves Up-Regulation of Nitric Oxide and a Favorable T Cell Response J. Immunol., March 15, 2001; 166(6): 4020 - 4028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Nickdel, F. Roberts, F. Brombacher, J. Alexander, and C. W. Roberts Counter-Protective Role for Interleukin-5 during Acute Toxoplasma gondii Infection Infect. Immun., February 1, 2001; 69(2): 1044 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Marshall, L. R. Brunet, Y. van Gessel, A. Alcaraz, S. K. Bliss, E. J. Pearce, and E. Y. Denkers Toxoplasma gondii and Schistosoma mansoni Synergize to Promote Hepatocyte Dysfunction Associated with High Levels of Plasma TNF-{alpha} and Early Death in C57BL/6 Mice J. Immunol., August 15, 1999; 163(4): 2089 - 2097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Silva, R. T. Gazzinelli, D. A. O. Silva, E. A. V. Ferro, L. H. Kasper, and J. R. Mineo Expression of Toxoplasma gondii-Specific Heat Shock Protein 70 during In Vivo Conversion of Bradyzoites to Tachyzoites Infect. Immun., August 1, 1998; 66(8): 3959 - 3963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Marshall and E. Y. Denkers Toxoplasma gondii Triggers Granulocyte-Dependent Cytokine-Mediated Lethal Shock in D-Galactosamine-Sensitized Mice Infect. Immun., April 1, 1998; 66(4): 1325 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Nasarre, J. L. Krahenbuhl, and T. R. Klei Down Regulation of Macrophage Activation in Brugia pahangi-Infected Jirds (Meriones unguiculatus) Infect. Immun., March 1, 1998; 66(3): 1063 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Yap, T. Scharton-Kersten, H. Charest, and A. Sher Decreased Resistance of TNF Receptor p55- and p75-Deficient Mice to Chronic Toxoplasmosis Despite Normal Activation of Inducible Nitric Oxide Synthase In Vivo J. Immunol., February 1, 1998; 160(3): 1340 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Johnson and P. C. Sayles Interleukin-12, Dendritic Cells, and the Initiation of Host-protective Mechanisms against Toxoplasma gondii J. Exp. Med., December 1, 1997; 186(11): 1799 - 1802. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
