Protective role of MyD88-independent innate immune responses against prion infection

Ishibashi, Daisuke; Atarashi, Ryuichiro; Nishida, Naoshi

doi:10.4161/pri.22579

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…, Ishibashi et al . ). Although the precise contribution of this molecule is not entirely understood, the results tend to indicate that MyD88 plays a key role in controlling infection, the immediate activation of the innate immune system, cytokine production and adaptive immune response activation in late stages (Koh et al .…”

Section: Introductionmentioning

confidence: 97%

MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils

et al. 2013

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Bezerra da Silva RA, Nelson-Filho P, Lucisano MP, De Rossi A, de Queiroz AM, Bezerra da Silva LA. Aim To characterize the formation and progression of experimentally induced periapical lesions in teeth of MyD88 knockout (MyD88 KO) mice compared with wild-type (WT) mice. Methodology Periapical lesions were induced in the mandibular first molars of 30 WT and 30 MyD88 KO mice. After 7, 21 and 42 days, the animals were euthanized and the mandibles were subjected to histotechnical processing. Histological sections were stained with haematoxylin and eosin (HE), TRAP histoenzymology, Brown and Brenn staining and immunohistochemistry (RANK, RANKL, OPG). Data were subjected to statistical analysis by the nonparametric Mann-Whitney and Kruskal-Wallis tests and the Dunn post-test, using the SPSS software, version 17.0 (a = 0.05). Results Regarding the periapical lesion size, the MyD88 KO group had significantly higher values than the WT group in the periods of 7 (P = 0.001) and 21 days (P = 0.05). A larger number of neutrophils in the MyD88 KO group were observed (P = 0.01 at 7 days, P = 0.004 at 21 days and P < 0.001 at 42 days). Regarding the number of osteoclasts, no statistically significant difference was observed between the groups at any of the experimental periods (P = 0.884 at 7 days, P = 0.506 at 21 days and P = 0.211 at 42 days). Conclusions In the absence of MyD88, the animals had larger periapical lesions, with a severe inflammatory infiltrate and a significantly larger number of neutrophils.

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Section: Introductionmentioning

confidence: 97%

MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils

et al. 2013

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“…MyD88 acts as a crucial downstream mediator of TLRs, and is involved in the recognition of danger signals and induction of the innate immune response (Ishibashi et al 2012;Warner and Nunez 2013). The TLR signaling pathway is the main component of the mammalian innate immune system (Yao et al 2009), and has also been identified in bony fish such as zebrafish, yellow croaker, and carp (Kongchum et al 2011;Meijer et al 2004;Qian et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of the myeloid differentiation factor 88 gene in yellow catfish

Zhang

Yang

et al. 2018

3 Biotech

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Myeloid differentiation factor 88 (MyD88) is an important adapter protein of the innate immune system, but it has never before been reported in yellow catfish (Pelteobagrus fulvidraco). In this study, we cloned and characterized the yellow catfish MyD88 gene. The gene was 1230 bp in length and contained an 876-bp open reading frame which encodes a polypeptide of 291 amino acid residues. The theoretical molecular mass and isoelectric point of this polypeptide were 33.4341 kDa and 5.17, respectively. Furthermore, bioinformatic and phylogenetic analyses grouped yellow catfish MyD88 with MyD88 of other fish. We found that the deduced amino acid sequence showed that the conserved N-terminal death domain and the C-terminal typical Toll/interleukin-1 receptor domain were very similar to those of other fish. Moreover, reverse transcription PCR showed that yellow catfish MyD88 is ubiquitously expressed in all tissues examined, with highest expression levels observed in the spleen and lowest levels in the intestine. Importantly, MyD88 was shown to be significantly up-regulated in the intestines after 30-day dietary supplement of Clostridium butyricum. Collectively, these results indicate that yellow catfish MyD88 has a conserved structure and is probably an important component of innate immunity in yellow catfish. This study is the first to identify and characterize MyD88 in yellow catfish, thereby providing a reference for further research into the yellow catfish innate immune system.

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“…Disrupted IRF-3 genes developed prion diseases earlier compared to wild-type mice after inoculation. Overexpression of IRF-3 significantly reduced the amount of abnormal prion protein in persistently infected cells, indicating that IRF-3 expression levels are closely related to the anti-prion state of the host cell 9,10 . Although the innate immune responses against prion invasion are insufficient to stop disease progression, involvement of IRF-3 inducible factors such as IFN-I may be one of the reasons why prion infection shows an extremely long incubation period.…”

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confidence: 91%

Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3

Homma

Ishibashi

Nakagaki

et al. 2014

Sci Rep

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As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.

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Protective role of MyD88-independent innate immune responses against prion infection

Cited by 9 publications

References 35 publications

MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils

MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils

Identification and characterization of the myeloid differentiation factor 88 gene in yellow catfish

Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3

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