Decrease in toll-like receptors 2 and 4 in the spleen of mouse with endotoxic tolerance

Zhong, Bei; Ying, Haoran; Yang, Qidong; Gu, Fei; Yin, Guo Qing; Xia, Chunmei

doi:10.1007/s00011-007-7104-4

Cited by 20 publications

(20 citation statements)

References 58 publications

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“…In several studies that have addressed the molecular basis of endotoxin tolerance, LPS unresponsiveness has been associated with decreased expression of NF-B (10), up-regulation of IL-1R-associated kinase-M (IRAK-M) (7,11), and SHIP (12), deregulation of TLR4 (13,14) or the immune signal amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) (9), and inhibition of IRAK-1 phosphorylation (15,16). The expression of IRAK-M has been pinpointed as a crucial factor in the control of this phenomenon (17), as previously suggested from analysis of IRAK-M Ϫ/Ϫ mice (18), and later shown by us in humans (7,11).…”

Section: E Ndotoxin Tolerance (Et)mentioning

confidence: 99%

Potent Phagocytic Activity with Impaired Antigen Presentation Identifying Lipopolysaccharide-Tolerant Human Monocytes: Demonstration in Isolated Monocytes from Cystic Fibrosis Patients

Fresno¹,

García‐Río

Gómez-Piña³

et al. 2009

The Journal of Immunology

193

192

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Monocyte exposure to LPS induces a transient state in which these cells are refractory to further endotoxin stimulation. This phenomenon, termed endotoxin tolerance (ET), is characterized by a decreased production of cytokines in response to the proinflammatory stimulus. We have established a robust model of ET and have determined the time frame and features of LPS unresponsiveness in cultured human monocytes. A large number of genes transcribed in tolerant monocytes were classified as either "tolerizable" or "nontolerizable" depending on their expression levels during the ET phase. Tolerant monocytes exhibit rapid IL-1R-associated kinase-M (IRAK-M) overexpression, high levels of triggering receptor expressed on myeloid cells-1 (TREM-1) and CD64, and a marked down-regulation of MHC molecules and NF-B2. These cells combine potent phagocytic activity with impaired capability for Ag presentation. We also show that circulating monocytes isolated from cystic fibrosis patients share all the determinants that characterize cells locked in an ET state. These findings identify a new mechanism that contributes to impaired inflammation in cystic fibrosis patients despite a high frequency of infections. Our results indicate that a tolerant phenotype interferes with timing, efficiency, and outcome of the innate immune responses against bacterial infections.

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Section: E Ndotoxin Tolerance (Et)mentioning

confidence: 99%

Potent Phagocytic Activity with Impaired Antigen Presentation Identifying Lipopolysaccharide-Tolerant Human Monocytes: Demonstration in Isolated Monocytes from Cystic Fibrosis Patients

Fresno¹,

García‐Río

Gómez-Piña³

et al. 2009

The Journal of Immunology

193

192

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“…Additionally, we noted that TLRs 2 and 4 mRNA in splenic MNCs were expressed significantly higher in newborn pigs than young and adult pigs (Figure 4B and 4D). Studies using SPF mice with intraperitoneal injection of LPS for 14 days showed a decrease of TLRs 2 and 4 protein expression in spleen (Zhong et al, 2008). Combined with our data showing that the TLRs 2 and 4 mRNA expression in splenic MNCs were unchanged in GF newborn and young pigs (Table 2), we assumed that the decrease of TLRs 2 and 4 expression might be mediated by the microbiota exposure after birth and during the weaning period.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific mRNA expression profiles of porcine Toll-like receptors at different ages in germ-free and conventional pigs

Shao

Fischer

Kandasamy

et al. 2016

Veterinary Immunology and Immunopathology

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Toll-like receptors (TLRs), key initiators of innate immune responses, recognize antigens and are essential in linking innate and adaptive immune responses. Misrecognition and over-stimulation/expression of TLRs may contribute to the development of chronic inflammatory diseases and autoimmune diseases. However, appropriate and mature TLR responses are associated with the establishment of resistance against some infectious diseases. In this study, we assessed the mRNA expression profile of TLRs 1-10 in splenic and ileal mononuclear cells (MNCs) and dendritic cells (DCs) of germ-free (GF) and conventional pigs at different ages. We found that the TLR mRNA expression profiles were distinct between GF and conventional pigs. The expression profiles were also significantly different between splenic and ileal MNCs/DCs. Comparison of the TLR expression profiles in GF and conventional newborn and young pigs demonstrated that exposure to commensal microbiota may play a more important role than age in TLR mRNA expression profiles. To our knowledge, this is the first report that systematically assesses porcine TLRs 1-10 mRNA expression profiles in MNCs and DCs from GF and conventional pigs at different ages. These results further highlighted that the commensal microbiota of neonates play a critical role through TLR signaling in the development of systemic and mucosal immune systems.

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“…LPS unresponsiveness has been associated with the upregulation of negative regulators like IRAK-M, ST2, SOCS1, short version of MyD88 (MyD88sh) [71,72,99,101] and SHIP [102] as well as the dysregulation of TLR4 [103] and the immune signal amplifier, Triggering receptor expressed in myeloid cells (TREM-1) [10,104]. Substantial differences in the mechanism governing endotoxin tolerance (ET) has been observed between human and mice models.…”

Section: Box 2 Negative Regulators and New Molecules In Endotoxin Tomentioning

confidence: 98%

Endotoxin tolerance: new mechanisms, molecules and clinical significance

Biswas

López‐Collazo

2009

Trends in Immunology

1,133

1,215

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Decrease in toll-like receptors 2 and 4 in the spleen of mouse with endotoxic tolerance

Abstract: TLR4 is the target of endotoxic tolerance induction. The induction of cross-tolerance of TLR2 following LPS challenge is present in vivo with endotoxin tolerance.

Cited by 20 publications

References 58 publications

Potent Phagocytic Activity with Impaired Antigen Presentation Identifying Lipopolysaccharide-Tolerant Human Monocytes: Demonstration in Isolated Monocytes from Cystic Fibrosis Patients

Potent Phagocytic Activity with Impaired Antigen Presentation Identifying Lipopolysaccharide-Tolerant Human Monocytes: Demonstration in Isolated Monocytes from Cystic Fibrosis Patients

Tissue-specific mRNA expression profiles of porcine Toll-like receptors at different ages in germ-free and conventional pigs

Endotoxin tolerance: new mechanisms, molecules and clinical significance

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