LPS stimulates and Hsp70 down-regulates TLR4 to orchestrate differential cytokine response of culture-differentiated innate memory CD8+ T cells

Ghosh, Amlan; Sinha, Debolina; Mukherjee, Subhadeep; Biswas, Ratna; Biswas, Tapas

doi:10.1016/j.cyto.2015.01.018

Cited by 25 publications

(18 citation statements)

References 56 publications

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“…In innate and adaptive immunity, LPS is recognized by LPS binding protein (LBP) and Toll-like receptor 4 (TLR4) to stimulate cytokine transcription (Park and Lee, 2013) as part of the recognition of pathogenassociated molecular patterns (PAMPs) (Kumagai and Akira, 2010), thus causing the LPS-induced inflammation. In T cells, TLR4-ligand LPS stimulated the TLR directing the cells toward type 1 polarization and expressed suppressor of cytokine signaling (SOCS) 1, and thus suppressed IL-10 expression (Ghosh et al, 2015). IL-10 was considered as a switch from tumor-promoting inflammation to antitumor immunity, and deficient IL-10 signaling developed tumors spontaneously and at high rates (Oft, 2014;Talero et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The Oral Microbiota May Have Influence on Oral Cancer

Zhang

Liu

Zheng

et al. 2020

Front. Cell. Infect. Microbiol.

249

212

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The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).

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Section: Discussionmentioning

confidence: 99%

The Oral Microbiota May Have Influence on Oral Cancer

Zhang

Liu

Zheng

et al. 2020

Front. Cell. Infect. Microbiol.

249

212

View full text Add to dashboard Cite

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“…Another essential question that remains was whether innate CD8 + cells arise from pre-existing conventional SP8 cells or from earlier stages in the T cell development. To test this question, we developed an in vitro model based on a previous report[48]. We sorted DP cells from B6 (WT) or OT-I control CD45.2 + mice and co-cultured them with the bulk population of thymocytes from either CD45.1 + control or CD45.1 + T .…”

Section: Resultsmentioning

confidence: 99%

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development

et al. 2019

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Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, the thymus experiences an enrichment of single positive CD8 (SP8) thymocytes that share all the established phenotypical and functional characteristics of innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significant increase in survival and a lower parasitemia in mice adoptively transferred with SP8 thymocytes from OT I—T. cruzi-infected mice, demonstrating that innate CD8+ thymocytes are able to protect against a lethal T. cruzi infection in an Ag-independent manner. Interestingly, we obtained similar results when using thymocytes from systemic IL-12 + IL-18-treated mice. This data indicates that cytokines triggered during the acute stage of a Th1 infectious process induce thymic production of IL-4 along with IL-15 expression resulting in an adequate niche for development of innate CD8+ T cells as early as the double positive (DP) stage. Our data demonstrate that the thymus can sense systemic inflammatory situations and alter its conventional CD8 developmental pathway when a rapid innate immune response is required to control different types of pathogens.

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“…Analysis of the isolated exosomes indicated that they were remarkably stable under both physiological and pathophysiological conditions[52]. If released from the exosomes, exHSP60 can be detrimental to cardiac myocytes via activation of TLR4[61]; there is evidence of other stress related proteins released in exosomes, but there is still debate about their adverse effects when extracellular [60, 62, 74–77]. Co-culture of adult murine cardiac myocytes with cardiac fibroblasts (CF) resulted in the development of cardiac myocyte hypertrophy[78, 79].…”

Section: Cardiac Exosomesmentioning

confidence: 99%

Exosomes as agents of change in the cardiovascular system

Poe

Knowlton

2017

Journal of Molecular and Cellular Cardiology

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Exosomes have an evolving role in paracrine and autocrine signaling, which is enhanced because these lipid vesicles are quite stable and can deliver miRNA, DNA, protein and other molecules to cells throughout the body. Most cell types release exosomes, and exosomes are found in all biological fluids, making them accessible biomarkers. Significantly, exosomes can carry a biologically potent cargo, which can alter the phenotype of recipient cells. In the cardiovascular system exosomes have been primarily studied for their role in mediating the beneficial effects of mesenchymal stem cells after myocardial injury. Exosomes released by cardiac cells in disease states, such as myocardial ischemia, can potentially have important pathophysiologic effects on other cardiac cells as well as on distant organs.

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LPS stimulates and Hsp70 down-regulates TLR4 to orchestrate differential cytokine response of culture-differentiated innate memory CD8+ T cells

Cited by 25 publications

References 56 publications

The Oral Microbiota May Have Influence on Oral Cancer

The Oral Microbiota May Have Influence on Oral Cancer

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development

Exosomes as agents of change in the cardiovascular system

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