Cited by 522Research on Leishmaniasis StudiesLeprosy Research and TreatmentImmune cells in cancer

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Tumor necrosis factor- alpha synergizes with IFN- gamma in mediating killing of Leishmania major through the induction of nitric oxide.

Liew, F Y, Li, Y, Millott, S·1990·The Journal of Immunology

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Abstract

CBA mice develop cutaneous lesions when infected with Leishmania major. The disease development was significantly reduced by injecting into the lesion a combination of rIFN-gamma and rTNF-alpha. The doses of IFN-gamma and TNF-alpha used were suboptimal in that either cytokine alone did not have any effect. The therapeutic effect of IFN-gamma and TNF-alpha in vivo is reflected in their ability to activate macrophages to kill the intracellular parasites in vitro. The macrophage leishmanicidal activity induced by TNF-alpha and IFN-gamma can be completely inhibited by a specific inhibitor (l-NG monomethyl arginine) of nitric oxide synthesis. There was a direct correlation between the intracellular killing of the parasites and the production of nitric oxide by the macrophages. In contrast, there was no correlation between leishmanicidal activity and superoxide production by macrophages.

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“The benefit of poly-functional T cells in protection against pathogens has been attributed by their: (a) ability to express higher levels of IFNγ on a per-cell basis than other populations (49, 57, 60, 64); (b) enhanced cytotoxicity due to secretion of both IFNγ and TNFα (65, 66); and (c) high IL-2-mediated proliferat…”
Background
High levels of nitric oxide production decrease early but increase late survival of Brucella abortus in macrophages
Wang, M., Qureshi, N., Soeurt, N., et al. (2001) · Microbial Pathogenesis · doi:10.1006/mpat.2001.0463 · Cited by 53
Local TH1 and TH2 responses to parasitic infection in the intestine: regulation by IFN-gamma and IL-4
Urban, J. F., Fayer, R., Sullivan, C. A., et al. (1996) · Veterinary Immunology and Immunopathology · doi:10.1016/s0165-2427(96)05708-x · Cited by 53
NF-κB1 Is Required for Optimal CD4+ Th1 Cell Development and Resistance to Leishmania major
Artis, D., Speirs, K. M., Joyce, K. L., Goldschmidt, M. H., Caamaño, J., Hunter, C. A., & Scott, P. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.1995 · Cited by 53
Importance of immunoglobulin E (IgE) in the protective mechanism against gastrointestinal nematode infection: looking at the intestinal mucosae
Negrão‐Corrêa, D. A. (2001) · Revista do Instituto de Medicina Tropical de São Paulo · doi:10.1590/s0036-46652001000500011 · Cited by 52
“The protective function of Th1 response was first characterized in Leishmania major infected mice (LIEW et al., 1990) and subsequently confirmed in Toxoplasma, Eimeria and Cryptosporidium infected mice (FINKELMAN & URBAN, 1992).”
Background
PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania
Santos, D. M., Carneiro, M. W., de Moura, T. R., Soto, M., Luz, N. F., Prates, D. B., Irache, J. M., Brodskyn, C. I., Barral, A. M. P., Barral‐Netto, M., et al. (2013) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2013.04.003 · Cited by 50
Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis
Carrillo, E., Ahmed, S. N., Goldsmith‐Pestana, K., et al. (2006) · Vaccine · doi:10.1016/j.vaccine.2006.10.036 · Cited by 51
“These higher levels of TNF-α are consistent with murine leishmaniasis model studies of both cutaneous and visceral diseases [58,59], where TNF-α has been shown to enhance the effects of IFN-γ in mediating parasite killing.”
Result
Immunomodulatory effect of Canova medication on experimental Leishmania amazonensis infection
Pereira, W. C. E., Lonardoni, M. V. C., Grespan, R., Caparroz‐Assef, S. M., Cuman, R. K. N., & Bersani-Amado, C. (2004) · Journal of Infection · doi:10.1016/j.jinf.2004.09.009 · Cited by 50
The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain
Ritter, U., Mattner, J., Rocha, J. S., Bogdan, C., & Körner, H. (2004) · Microbes and Infection · doi:10.1016/j.micinf.2004.02.008 · Cited by 53
Roles of Nitric Oxide in Surgical Infection and Sepsis
Johnson, M. L., & Billiar, T. R. (1998) · World Journal of Surgery · doi:10.1007/s002689900368 · Cited by 50
Characterization of Glycolytic Enzymes - rAldolase and rEnolase of Leishmania donovani, Identified as Th1 Stimulatory Proteins, for Their Immunogenicity and Immunoprophylactic Efficacies against Experimental Visceral Leishmaniasis
Gupta, R., Kumar, V., Kushawaha, P. K., Tripathi, C. D. P., Joshi, S. A., Sahasrabuddhe, A. A., Mitra, K., Sundar, S., Siddiqi, M. I., & Dube, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086073 · Cited by 50
“Transcripts of IFN-c and TNF-a, often reported to act in concert to activate iNOS for the production of NO [79], showed manifold increase in all the immunized groups of hamsters.”
Background
Interferon‐gamma and resistance to bacterial infections
Czarniecki, C. W., & Sonnenfeld, G. (1993) · Apmis · doi:10.1111/j.1699-0463.1993.tb00073.x · Cited by 50
“89); and production of effector molecules such as toxic oxygen and nitrogen intermediates (1, 2, 5 , 30, 31, 34, 37, 38, 49, 62, 63, 72, 113).”
Background
Phagocytosis enhances murine macrophage activation by interferon‐γ and tumor necrosis factor‐α
Corradin, S. B., Buchmüller-Rouiller, Y., & Mauël, J. (1991) · European Journal of Immunology · doi:10.1002/eji.1830211036 · Cited by 49
Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response
Nico, D., Claser, C., Borja-Cabrera, G. P., et al. (2010) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000866 · Cited by 49
Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis
Kushawaha, P. K., Gupta, R., Tripathi, C. D. P., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035670 · Cited by 49
“The transcript of IFN-c, a signature cytokine of the Th1-type response having a dominant effect on macrophage microbicidal responses and other effector killing mechanisms, along with TNF-a, often reported to act in concert to activate iNOS for the production of NO [75,76], were found to be down-regulated [64] in infec…”
Background
Susceptibility to Intracellular Infections: Contributions of TNF to Immune Defense
Li, X., Körner, H., & Liu, X. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01643 · Cited by 49
Role ofLeishmania donovaniand Its Lipophosphoglycan in CD4+T-cell Activation-Induced Human Immunodeficiency Virus Replication
Wolday, D., Akuffo, H., Demissie, A., et al. (1999) · Infection and Immunity · doi:10.1128/iai.67.10.5258-5264.1999 · Cited by 49
“Although TNF-a has been shown to mediate host protection against Leishmania (14), its uncontrolled production may result in pathology.”
Background
Structure and biological activities of acapsular Cryptococcus neoformans 602 complemented with the CAP64 gene
Chang, Y. C., Cherniak, R., Kozel, T. R., Granger, D. L., Morris, L., Weinhold, L. C., & Kwon-Chung, K. J. (1997) · Infection and Immunity · doi:10.1128/iai.65.5.1584-1592.1997 · Cited by 48
“, IFN-g) with a microorganism results in synergism for cytotoxic functions, especially nitric oxide-mediated cytotoxicity (22).”
Background
Antimicrobial Properties of Nitric Oxide
DeGroote, M. A., & Fang, F. C. (2002) · Springer eBooks · doi:10.1007/0-306-46816-6_12 · Cited by 55
Soluble TNF and membrane TNF expressed on CD4+ T lymphocytes differ In their ability to activate macrophage antileishmanial defense
Birkland, T. P., Sypek, J. P., & Wyler, D. J. (1992) · Journal of Leukocyte Biology · doi:10.1002/jlb.51.3.296 · Cited by 49
Antigen Presentation by Macrophages Harboring Intravesicular Pathogens
Overath, P., & Aebischer, T. (1999) · Parasitology Today · doi:10.1016/s0169-4758(99)01473-8 · Cited by 48
An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection
Allenbach, C., Launois, P., Mueller, C., & Tacchini‐Cottier, F. (2008) · European Journal of Immunology · doi:10.1002/eji.200737662 · Cited by 48
Tumour Necrosis Factor and Associated Cytokines in the host's response to malaria
Richards, A. L. (1997) · International Journal for Parasitology · doi:10.1016/s0020-7519(97)00122-7 · Cited by 48
Role of TNF-α in the Induction of Fungicidal Activity of Mouse Peritoneal Exudate Cells againstCryptococcus neoformansby IL-12 and IL-18
Kawakami, K., Qureshi, M. H., Koguchi, Y., et al. (1999) · Cellular Immunology · doi:10.1006/cimm.1999.1460 · Cited by 48
Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections
Nahrevanian, H. (2009) · The Brazilian Journal of Infectious Diseases · doi:10.1590/s1413-86702009000600010 · Cited by 47

Authors: Liew, F. Y., Li, Y., & Millott, S.
Affiliations: Wellcome Trust (GB)
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1990-12
Volume: 145
Issue: 12
Pages: 4306-4310
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.145.12.4306
OpenAlex: W1739247159
Cited by: 522
References: 0
Citations by year: 2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 9 · 2020: 16 · 2019: 7 · 2018: 14 · 2017: 16 · 2016: 11 · 2015: 13 · 2014: 21 · 2013: 16 · 2012: 15
FWCI: 37.31
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: Leishmania major, cutaneous leishmaniasis, TNF-α, interferon-gamma, nitric oxide, macrophage activation, antileishmanial activity, L-NG-monomethylarginine, superoxide, cytokine synergy
MeSH terms: Animals, Arginine, Cytotoxicity, Immunologic, Drug Synergism, Hydrogen Peroxide, Immunity, Cellular, Interferon-gamma, Leishmania tropica, Leishmaniasis, Macrophages, Mice, Inbred CBA, Nitric Oxide, Nitrites, Superoxides, Tumor Necrosis Factor-alpha, omega-N-Methylarginine, Mice

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Tumor necrosis factor- alpha synergizes with IFN- gamma in mediating killing of Leishmania major through the induction of nitric oxide.

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