Tumor necrosis factor‐α in combination with interferon‐γ, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes

Bogdan, Christian; Moll, Heidrun; Solbach, Werner; Röllinghoff, Martin

doi:10.1002/eji.1830200528

Cited by 183Research on Leishmaniasis StudiesLeprosy Research and TreatmentParasites and Host Interactions

Tumor necrosis factor‐α in combination with interferon‐γ, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes

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Bogdan, Christian, Moll, Heidrun, Solbach, Werner, Röllinghoff, Martin·1990·European Journal of Immunology

DOI 10.1002/eji.1830200528

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Abstract

We have previously shown that during an infection with Leishmania major, susceptible BALB/c mice, as opposed to mice of a resistant strain (C57BL/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor‐α (TNF‐α) which is known to be a potent macrophage (MΦ) stimulator in other parasitic diseases. In the present study we investigated whether TNF‐α activates MΦ for killling of L. major parasites. In the absence of interferon‐γ (IFN‐γ) or lipopolysaccharide, TNF‐α (0.025—25000 U/ml) failed to activate peritoneal exudate MΦ from BALB/c micefor killling of L. major amastigotes. In the presence of suboptimal doses of IFN‐γ (5 or 10 U/ml), however, TNF‐α mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN‐γ alone. The combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conclude that thepresence of IFN‐γ is curcial for TNF‐α‐mediated killing of L. major parasites by MΦ. Disease progression in susceptible mice thereforeseems to be a consequence of a deficiency of IFN‐γ and a predominance of interleukin 4 rather than the result of an excess amount of TNF‐α.

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IFNγ co-operates with other TH1 cell cytokines and acts synergistically to enhance their ability to eliminate pathogens.
“It is worth noting that IFNγ co-operates with other TH1 cell cytokines and acts synergistically to enhance their ability to eliminate pathogens31,32.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [31]
Section 3.2 reports a synergistic anti-parasitic effect of IFN-γ and TNF-α: together they reduced L. major parasites in murine macrophages when either cytokine alone was ineffective at the tested doses. The Concluding remarks suggest this synergy may matter for protection against other intracellular parasites, but the paper does not establish synergy with TH1 cytokines generally or elimination of pathogens generally. (LLM, conf=0.84)
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Authors: Bogdan, C., Moll, H., Solbach, W., & Röllinghoff, M.
Affiliations: Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Corresponding author: Bogdan, Christian
ORCID: Bogdan, Christian
Moll, Heidrun
Solbach, Werner
Venue: European Journal of Immunology
Publisher: Wiley
Published: 1990-05
Volume: 20
Issue: 5
Pages: 1131-1135
ISSN: 0014-2980 (ISSN-L)
1521-4141
DOI: 10.1002/eji.1830200528
OpenAlex: W2081798138
Cited by: 183
References: 38
Citations by year: 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 1 · 2018: 10 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 7
FWCI: 19.49
Type: journal article
Language: en
Open access: green
opus.bibliothek.uni-wuerzburg.de
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5679 d)
Locations: European Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Online Publication Service of Würzburg University (Würzburg University) (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft
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 › Parasitology › Parasites and Host Interactions
Keywords: TNF-α, interferon-gamma, IL-4, macrophage activation, Leishmania major, amastigotes, peritoneal macrophages, lipopolysaccharide, BALB/c mice, C57BL/6 mice, host-parasite interactions
MeSH terms: Animals, Drug Interactions, Female, Interferon-gamma, Kinetics, Leishmania tropica, Macrophages, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Interleukin-4, Mice, In Vitro Techniques

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Tumor necrosis factor‐α in combination with interferon‐γ, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes

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