Abstract
Recombinant human tumor necrosis factor (TNF) and purified murine TNF were both able to activate macrophages to destroy intracellular Leishmania major in vitro. In addition, parasitizing macrophages with L. major markedly increased the ability of the cells to produce TNF. Finally, when mice were vaccinated with an avirulent form of L. major, the animals produced large amounts of TNF but no gamma interferon in response to infection with virulent L. major. Treating these mice with a neutralizing anti-TNF antibody led to partial but not complete inhibition of the resistant state, which suggests that factors other than TNF and gamma interferon contribute to resistance to L. major.
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Selected References
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- Belosevic M., Finbloom D. S., Van Der Meide P. H., Slayter M. V., Nacy C. A. Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J Immunol. 1989 Jul 1;143(1):266–274. [PubMed] [Google Scholar]
- Beutler B., Cerami A. Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem. 1988;57:505–518. doi: 10.1146/annurev.bi.57.070188.002445. [DOI] [PubMed] [Google Scholar]
- Bogdan C., Moll H., Solbach W., Röllinghoff M. Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. Eur J Immunol. 1990 May;20(5):1131–1135. doi: 10.1002/eji.1830200528. [DOI] [PubMed] [Google Scholar]
- Boom W. H., Liebster L., Abbas A. K., Titus R. G. Patterns of cytokine secretion in murine leishmaniasis: correlation with disease progression or resolution. Infect Immun. 1990 Dec;58(12):3863–3870. doi: 10.1128/iai.58.12.3863-3870.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerami A., Beutler B. The role of cachectin/TNF in endotoxic shock and cachexia. Immunol Today. 1988 Jan;9(1):28–31. doi: 10.1016/0167-5699(88)91353-9. [DOI] [PubMed] [Google Scholar]
- Corradin S. B., Mauël J. Phagocytosis of Leishmania enhances macrophage activation by IFN-gamma and lipopolysaccharide. J Immunol. 1991 Jan 1;146(1):279–285. [PubMed] [Google Scholar]
- Green L. M., Reade J. L., Ware C. F. Rapid colorimetric assay for cell viability: application to the quantitation of cytotoxic and growth inhibitory lymphokines. J Immunol Methods. 1984 May 25;70(2):257–268. doi: 10.1016/0022-1759(84)90190-x. [DOI] [PubMed] [Google Scholar]
- Green S. J., Crawford R. M., Hockmeyer J. T., Meltzer M. S., Nacy C. A. Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. J Immunol. 1990 Dec 15;145(12):4290–4297. [PubMed] [Google Scholar]
- Liew F. Y., Li Y., Millott S. Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J Immunol. 1990 Dec 15;145(12):4306–4310. [PubMed] [Google Scholar]
- Liew F. Y., Parkinson C., Millott S., Severn A., Carrier M. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis. Immunology. 1990 Apr;69(4):570–573. [PMC free article] [PubMed] [Google Scholar]
- Marchand M., Daoud S., Titus R. G., Louis J., Boon T. Variants with reduced virulence derived from Leishmania major after mutagen treatment. Parasite Immunol. 1987 Jan;9(1):81–92. doi: 10.1111/j.1365-3024.1987.tb00490.x. [DOI] [PubMed] [Google Scholar]
- McGurn M., Boon T., Louis J. A., Titus R. G. Leishmania major: nature of immunity induced by immunization with a mutagenized avirulent clone of the parasite in mice. Exp Parasitol. 1990 Jul;71(1):81–89. doi: 10.1016/0014-4894(90)90010-a. [DOI] [PubMed] [Google Scholar]
- Moll H., Binöder K., Bogdan C., Solbach W., Röllinghoff M. Production of tumour necrosis factor during murine cutaneous leishmaniasis. Parasite Immunol. 1990 Sep;12(5):483–494. doi: 10.1111/j.1365-3024.1990.tb00983.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Murray H. W., Stern J. J., Welte K., Rubin B. Y., Carriero S. M., Nathan C. F. Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. J Immunol. 1987 Apr 1;138(7):2290–2297. [PubMed] [Google Scholar]
- Nacy C. A., Fortier A. H., Meltzer M. S., Buchmeier N. A., Schreiber R. D. Macrophage activation to kill Leishmania major: activation of macrophages for intracellular destruction of amastigotes can be induced by both recombinant interferon-gamma and non-interferon lymphokines. J Immunol. 1985 Nov;135(5):3505–3511. [PubMed] [Google Scholar]
- Sacks D. L., Perkins P. V. Identification of an infective stage of Leishmania promastigotes. Science. 1984 Mar 30;223(4643):1417–1419. doi: 10.1126/science.6701528. [DOI] [PubMed] [Google Scholar]
- Sadick M. D., Heinzel F. P., Holaday B. J., Pu R. T., Dawkins R. S., Locksley R. M. Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990 Jan 1;171(1):115–127. doi: 10.1084/jem.171.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherry B. A., Gelin J., Fong Y., Marano M., Wei H., Cerami A., Lowry S. F., Lundholm K. G., Moldawer L. L. Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models. FASEB J. 1989 Jun;3(8):1956–1962. doi: 10.1096/fasebj.3.8.2721856. [DOI] [PubMed] [Google Scholar]
- Squires K. E., Schreiber R. D., McElrath M. J., Rubin B. Y., Anderson S. L., Murray H. W. Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response. J Immunol. 1989 Dec 15;143(12):4244–4249. [PubMed] [Google Scholar]
- Titus R. G., Ceredig R., Cerottini J. C., Louis J. A. Therapeutic effect of anti-L3T4 monoclonal antibody GK1.5 on cutaneous leishmaniasis in genetically-susceptible BALB/c mice. J Immunol. 1985 Sep;135(3):2108–2114. [PubMed] [Google Scholar]
- Titus R. G., Chiller J. M. Orally induced tolerance. Definition at the cellular level. Int Arch Allergy Appl Immunol. 1981;65(3):323–338. [PubMed] [Google Scholar]
- Titus R. G., Kelso A., Louis J. A. Intracellular destruction of Leishmania tropica by macrophages activated with macrophage activating factor/interferon. Clin Exp Immunol. 1984 Jan;55(1):157–165. [PMC free article] [PubMed] [Google Scholar]
- Titus R. G., Marchand M., Boon T., Louis J. A. A limiting dilution assay for quantifying Leishmania major in tissues of infected mice. Parasite Immunol. 1985 Sep;7(5):545–555. doi: 10.1111/j.1365-3024.1985.tb00098.x. [DOI] [PubMed] [Google Scholar]
- Titus R. G., Sherry B., Cerami A. Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. J Exp Med. 1989 Dec 1;170(6):2097–2104. doi: 10.1084/jem.170.6.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]