Pro-inflammatory Cytokine Expression of Spleen Dendritic Cells in Mouse Toxoplasmosis

Nam, Ho Woo; Ahn, Hye Jin; Yang, Hyun

doi:10.3347/kjp.2011.49.2.109

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…In both experimental models, Ifnγ, Il1β, and Tlr4 were upregulated in the spleen ( Figure 1 and Figure 2 ). This is in line with previous reports describing increased splenic expression of these genes after T. gondii infection [ 4 , 14 , 28 , 29 , 30 ]. In human monocytes, particularly the secreted GRA15 protein of T. gondii is responsible for IL-1β induction and the release of IL-1β is a direct consequence of inflammasome activation after infection [ 31 ].…”

Section: Discussionsupporting

confidence: 93%

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

Znalesniak

Salm

et al. 2017

IJMS

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The spleen plays an important role in coordinating both adaptive and innate immune responses. Here, the transcriptional response to T. gondii infection in the murine spleen was characterized concerning inflammasome sensors (two different models: seven days after oral or four weeks after intraperitoneal infection). Additionally, Tff1KO and Tff3KO mice were investigated because TFF genes are often upregulated during inflammation. The expression of the pattern-recognition receptors Nlrp3, Nlrp12, and Nlrp1a was significantly increased after infection. This increase was diminished in Tff1KO and Tff3KO mice pointing towards a positive regulation of the inflammatory response by Tff1 and Tff3. Furthermore, the transcription of Tff1 (encoding a motogenic lectin) and other secretory genes was analyzed, i.e., gastrokines (Gkn), IgG Fc binding protein (Fcgbp), and the mucin Muc2. The corresponding gene products belong to an interactome protecting mucous epithelia. Tff1 was significantly induced after infection, which might increase the motility of immune cells. In contrast, Gkn3, Fcgbp, and Muc2 were downregulated seven days after oral infection; whereas four weeks after i.p. infection only Gkn3 remained downregulated. This might be an indication that Gkn3, Fcgbp, and Muc2 are involved in the transient disruption of the splenic architecture and its reorganization, which is characteristic after T. gondii infection.

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Section: Discussionsupporting

confidence: 93%

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

Znalesniak

Salm

et al. 2017

IJMS

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“…Mature DCs secrete inflammatory cytokines (IL-12, IL-1β, and TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β) and present antigens to naïve T-cells for activation [6,16]. In this regard, as previously reported, the production of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, IL-10, and TNF-α, was significantly increased in the BALB/c mouse splenic CD11c + DCs at week 1 post-infection [17]. It has been shown that in response to stimulation with Toxoplasma antigens or live parasites, the T-cells derived from the C57BL/6 mice preferentially produced Th1 cytokines with high IFN-γ and low IL-4 levels, whereas those from the BALB/c mice typically produced Th2 cytokines with low IFN-γ and high IL-4 levels [3,18].…”

Section: Discussionsupporting

confidence: 74%

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice

Lee

Yuk

Cha

et al. 2023

Parasites Hosts Dis

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Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

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“…In contrast, LPS stimulated BMDCs had elevated levels of many transcripts associated with MHC I and II complex. Additionally, T. gondii infected BMDCs had congruent elevated expression of both mRNA and protein levels of pro-inflammatory cytokines IL-1α, IL-12, and IL-6 (Nam et al, 2011). These data validate the model of infection and the multi-omics approach where metabolomic, transcriptomic data and functional studies can complement, be related to, and add value to each other.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Studies Demonstrate Toxoplasma gondii-Induced Metabolic Reprogramming of Murine Dendritic Cells

Hargrave

Woods

Millington

et al. 2019

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is capable of actively invading almost any mammalian cell type including phagocytes. Early events in phagocytic cells such as dendritic cells are not only key to establishing parasite infection, but conversely play a pivotal role in initiating host immunity. It is now recognized that in addition to changes in canonical immune markers and mediators, alteration in metabolism occurs upon activation of phagocytic cells. These metabolic changes are important for supporting the developing immune response, but can affect the availability of nutrients for intracellular pathogens including T. gondii. However, the interaction of T. gondii with these cells and particularly how infection changes their metabolism has not been extensively investigated. Herein, we use a multi-omics approach comprising transcriptomics and metabolomics validated with functional assays to better understand early events in these cells following infection. Analysis of the transcriptome of T. gondii infected bone marrow derived dendritic cells (BMDCs) revealed significant alterations in transcripts associated with cellular metabolism, activation of T cells, inflammation mediated chemokine and cytokine signaling pathways. Multivariant analysis of metabolomic data sets acquired through non-targeted liquid chromatography mass spectroscopy (LCMS) identified metabolites associated with glycolysis, the TCA cycle, oxidative phosphorylation and arginine metabolism as major discriminants between control uninfected and T. gondii infected cells. Consistent with these observations, glucose uptake and lactate dehydrogenase activity were upregulated in T. gondii infected BMDC cultures compared with control BMDCs. Conversely, BMDC mitochondrial membrane potential was reduced in T. gondii-infected cells relative to mitochondria of control BMDCs. These changes to energy metabolism, similar to what has been described following LPS stimulation of BMDCs and macrophages are often termed the Warburg effect. This metabolic reprogramming of cells has been suggested to be an important adaption that provides energy and precursors to facilitate phagocytosis, antigen processing and cytokine production. Other changes to BMDC metabolism are evident following T. gondii infection and include upregulation of arginine degradation concomitant with increased arginase-1 activity and ornithine and proline production. As T. gondii is an arginine auxotroph the resultant reduced cellular arginine levels are likely to curtail parasite multiplication. These results highlight the complex interplay of BMDCs and parasite metabolism within the developing immune response and the consequences for adaptive immunity and pathogen clearance.

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Pro-inflammatory Cytokine Expression of Spleen Dendritic Cells in Mouse Toxoplasmosis

Cited by 7 publications

References 21 publications

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice

Multi-Omics Studies Demonstrate Toxoplasma gondii-Induced Metabolic Reprogramming of Murine Dendritic Cells

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