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Cited by 116Toxoplasma gondii Research StudiesImmune Cell Function and InteractionT-cell and B-cell Immunology

Interleukin-18 (IL-18) Enhances Innate IL-12-Mediated Resistance to Toxoplasma gondii

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Cai, Guifang, Kastelein, Robert, Hunter, Christopher A.·2000·Infection and Immunity
DOI 10.1128/iai.68.12.6932-6938.2000PMC PMC97801
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Abstract

Innate resistance to Toxoplasma gondii is dependent on the ability of interleukin-12 (IL-12) to stimulate natural killer (NK) cell production of gamma interferon (IFN-γ). Since IL-18 is a potent enhancer of IL-12-induced production of IFN-γ by NK cells, SCID mice (which lack an adaptive immune response) were used to assess the role of IL-18 in innate resistance to T. gondii. Administration of anti-IL-18 to SCID mice infected with T. gondii resulted in an early reduction in serum levels of IFN-γ but did not significantly decrease resistance to this infection. In contrast, administration of exogenous IL-18 to infected SCID mice resulted in increased production of IFN-γ, reduced parasite burden, and a delay in time to death. The protective effects of IL-18 treatment correlated with increased NK cell numbers and cytotoxic activity at the local site of administration and with elevated levels of inducible nitrous oxide synthose in the spleens of treated mice. In addition, in vivo depletion studies demonstrated that the ability of exogenous IL-18 to enhance resistance to T. gondii was dependent on IL-12, IFN-γ, and NK cells. Together, these studies demonstrate that although endogenous IL-18 appears to have a limited role in innate resistance to T. gondii, treatment with IL-18 can augment NK cell-mediated immunity to this pathogen.

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  • TLR4 signaling is key in driving proinflammatory responses associated with COVID-19 and contributes to an increased Th1-type immune response because IL-18 (and IL-1β) strongly induces IFNs.

    “TLR4 signaling is key in driving proinflammatory responses associated with COVID-19 and contributes to an increased Th1-type immune response because IL-18 (and IL-1 β ) strongly induces IFNs. 143-145”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [144]

    The Results (page not provided) show that IL-18 enhanced IFN-γ production in cells from T. gondii-infected mice, largely in an IL-12-dependent manner. The paper does not establish that IL-1β induces interferons or that TLR4 signaling drives proinflammatory responses and a Th1-type response in COVID-19. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • IL-18 strongly drives Th1 immune responses, but in BALB/c mice, this produces a mixed Th1/Th2 response that promotes fibrosis and DCM rather than a classical STAT-driven Th1 response.

    “IL-18, originally named IFNγ -inducing factor, strongly drives Th1 immune responses, 143-145 but in BALB/c mice, this produces a mixed Th1/Th2 response that promotes fibrosis and DCM rather than a classical STAT-driven Th1 respo nse. 115,146,160,165”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [144]

    The Results report that IL-18 enhanced IFN-γ production in infected mice, especially alongside IL-12, supporting the sentence’s general point about a type 1 immune response. The paper does not report a mixed Th1/Th2 response in BALB/c mice or link IL-18 to fibrosis or DCM; its STAT4 discussion concerns resistance to toxoplasmosis, not that cardiac outcome. (LLM, conf=0.83)

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Sorted by citations

Authors
Cai, G., Kastelein, R., & Hunter, C. A.
Affiliations
  • University of Pennsylvania (US)
  • <!--label omitted: 2-->Department of Molecular Biology, DNAX Research Institute, Palo Alto, California2
ORCID
Venue
Infection and Immunity
Publisher
American Society for Microbiology
Published
2000-12
Volume
68
Issue
12
Pages
6932-6938
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
DOI
10.1128/iai.68.12.6932-6938.2000
PMC
PMC97801
OpenAlex
W2170091723
Cited by
116
References
1
Citations by year
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FWCI
9.32
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Infection and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI-42334-01, R01AI042334)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK50306, P30DK050306)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
IL-18, IL-12, Toxoplasma gondii, toxoplasmosis, innate immunity, natural killer cells, interferon-gamma, NK cell cytotoxicity, inducible nitric oxide synthase, SCID mice, infection intensity, cytokine synergy
MeSH terms
Animals, Interferon-gamma, Killer Cells, Natural, Toxoplasmosis, Animal, Mice, SCID, Interleukin-12, Interleukin-18, Mice

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