DOI: 10.4049/jimmunol.169.7.3863. Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance of<i>Listeria monocytogenes</i>in Mice

Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance ofListeria monocytogenesin Mice

10.4049/jimmunol.169.7.3863

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

AbstractListeria monocytogenes (LM), a facultative intracellular Gram-positive bacterium, often causes lethal infection of the host. In this study we investigated the molecular mechanism underlying LM eradication in the early phase of infection. Upon infection with LM, both IL-12 and IL-18 were produced, and then they synergistically induced IFN-γ production, leading to normal LM clearance in the host. IFN-γ knockout (KO) mice were highly susceptible to LM infection. IL-12/IL-18 double knockout mice were also highly susceptible. Their susceptibility was less than that of IFN-γ KO mice, but more than that of single IL-12 or IL-18 KO mice. Mice deficient in myeloid differentiation factor 88 (MyD88), an essential adaptor molecule used by signal transduction pathways of all members of the Toll-like receptor (TLR) family, showed an inability to produce IL-12 and IFN-γ following LM infection and were most susceptible to LM. Furthermore, MyD88-deficient, but not IFN-γ-deficient, Kupffer cells could not produce TNF-α in response to LM in vitro, indicating the importance of MyD88-dependent TNF-α production for host defense. As TLR2 KO, but not TLR4 KO, mice showed partial impairment in their capacity to produce IL-12, IFN-γ, and TNF-α, TLR2 activation partly contributed to the induction of IL-12-mediated IFN-γ production. These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-α production and for IL-12- and IL-18-mediated IFN-γ production in early phase clearance of LM.

Bibliography

Seki, E., Tsutsui, H., Tsuji, N. M., Hayashi, N., Adachi, K., Nakano, H., Futatsugi-Yumikura, S., Takeuchi, O., Hoshino, K., Akira, S., Fujimoto, J., & Nakanishi, K. (2002). Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance ofListeria monocytogenesin Mice. The Journal of Immunology, 169(7), 3863â3868.

Authors 12

Ekihiro Seki (first)
Hiroko Tsutsui (additional)
Noriko M. Tsuji (additional)
Nobuki Hayashi (additional)
Keishi Adachi (additional)
Hiroki Nakano (additional)
Shizue Futatsugi-Yumikura (additional)
Osamu Takeuchi (additional)
Katsuaki Hoshino (additional)
Shizuo Akira (additional)
Jiro Fujimoto (additional)
Kenji Nakanishi (additional)

References 35 Referenced 222

Dates

Type	When
Created	11 years, 4 months ago (April 21, 2014, 7:18 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 11:50 a.m.)
Indexed	2 weeks, 2 days ago (Aug. 12, 2025, 5:55 p.m.)
Issued	22 years, 10 months ago (Oct. 1, 2002)
Published	22 years, 10 months ago (Oct. 1, 2002)
Published Print	22 years, 10 months ago (Oct. 1, 2002)

Funders 0

None

BibTeX

@article{Seki_2002, title={Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance ofListeria monocytogenesin Mice}, volume={169}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.169.7.3863}, DOI={10.4049/jimmunol.169.7.3863}, number={7}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Seki, Ekihiro and Tsutsui, Hiroko and Tsuji, Noriko M. and Hayashi, Nobuki and Adachi, Keishi and Nakano, Hiroki and Futatsugi-Yumikura, Shizue and Takeuchi, Osamu and Hoshino, Katsuaki and Akira, Shizuo and Fujimoto, Jiro and Nakanishi, Kenji}, year={2002}, month=oct, pages={3863–3868} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>Listeria monocytogenes (LM), a facultative intracellular Gram-positive bacterium, often causes lethal infection of the host. In this study we investigated the molecular mechanism underlying LM eradication in the early phase of infection. Upon infection with LM, both IL-12 and IL-18 were produced, and then they synergistically induced IFN-\u03b3 production, leading to normal LM clearance in the host. IFN-\u03b3 knockout (KO) mice were highly susceptible to LM infection. IL-12/IL-18 double knockout mice were also highly susceptible. Their susceptibility was less than that of IFN-\u03b3 KO mice, but more than that of single IL-12 or IL-18 KO mice. Mice deficient in myeloid differentiation factor 88 (MyD88), an essential adaptor molecule used by signal transduction pathways of all members of the Toll-like receptor (TLR) family, showed an inability to produce IL-12 and IFN-\u03b3 following LM infection and were most susceptible to LM. Furthermore, MyD88-deficient, but not IFN-\u03b3-deficient, Kupffer cells could not produce TNF-\u03b1 in response to LM in vitro, indicating the importance of MyD88-dependent TNF-\u03b1 production for host defense. As TLR2 KO, but not TLR4 KO, mice showed partial impairment in their capacity to produce IL-12, IFN-\u03b3, and TNF-\u03b1, TLR2 activation partly contributed to the induction of IL-12-mediated IFN-\u03b3 production. These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-\u03b1 production and for IL-12- and IL-18-mediated IFN-\u03b3 production in early phase clearance of LM.</jats:p>",
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