The Chemokine System in Innate Immunity

Chronic diseases are often associated with altered inflammatory response, leading to increased host vulnerability to new inflammatory challenges. Employing streptozotocin (STZ)-induced diabetes as a model, we further investigate mechanisms leading to enhanced neutrophil (polymorphonuclear leukocytes, PMN) response under hyperglycemia and compare to that under chronic colitis. We show that, different from colitis under which PMN response is significantly potentiated, the existence of a proinflammatory state associated with broad increases in macrophages in various organs plays a dominant role in promoting PMN inflammatory response in diabetic mice. Studies of PMN infiltration during zymosan-induced peritonitis reveal that hyperglycemia enhances PMN recruitment not through inducing a high level of IL-17, which is the case in colitis, but through increasing F4/80+ macrophages in the peritoneal cavity, resulting in elevations of IL-6, IL-1β, TNF-α, and CXCL1 production. Insulin reversal of hyperglycemia, but not the neutralization of IL-17, reduces peritoneal macrophage numbers and ameliorates PMN infiltration during peritonitis. Significantly increased macrophages are also observed in the liver, kidneys, and intestines under hyperglycemia, and are attributable to exacerbated nephropathy and colitis when inflammatory conditions are induced by doxorubicin and dextran sulfate sodium (DSS), respectively. Furthermore, analyses of monocyte production and macrophage proliferation in tissues suggest significant monocytosis of inflammatory F4/80+Gr-1+ monocytes from the spleen and macrophage proliferation in situ synergistically contribute to the increased macrophage population under hyperglycemia. In conclusion, our results demonstrate that STZ-induced hyperglycemic mice develop a systemic proinflammatory state mediated by broad infiltration of macrophages.

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“…tissue macrophages) respond to infection and/or injury, and produce potent proinflammatory mediators (1–4). These mediators (i.e.…”

Section: Introductionmentioning

confidence: 99%

Broad Infiltration of Macrophages Leads to a Proinflammatory State in Streptozotocin-Induced Hyperglycemic Mice

Niu

Bian

Tremblay

et al. 2016

The Journal of Immunology

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“…in different tissues. [10][11][12][13] This chemokine-GAG interaction is thought to occur between, for example, sulphated domains of GAGs and basic amino acid motifs (GAGbinding motifs) of chemokines to ensure a high local concentration of the produced chemokines and to prevent chemokine diffusion and degradation, thereby creating a haptotactic gradient on the vascular endothelial cells at the site of inflammation. Therefore, GAGs play a major role in cell signalling and development, cell proliferation, angiogenesis, tumour progression, metastasis and anticoagulation.…”

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confidence: 99%

Anti‐inflammatory effects of the GAG‐binding CXCL9(74‐103) peptide in dinitrofluorobenzene‐induced contact hypersensitivity in mice

Vanheule

Crijns

Poosti

et al. 2018

Clin Experimental Allergy

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“…ment factors [7][8][9] , alarmins [10,11] , cytokines/chemokines [12] , chitinases/chitinase-like proteins [13] , acutephase proteins, proteases, and other less-categorized molecules. Innate immune responses are typically rapid and can be triggered without the selective events that underlie adaptive immunity, which is characterized by antigen-specificity and immunological memory.…”

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confidence: 99%

“…Attracted by chemokine gradients, innate immune cells migrate into the infected target organ [28] . Chemokines recruit innate immune cells through cognate G-proteincoupled chemokine receptors to sites of inflammation, and are termed according to their first cysteine residues into C, C-C, C-X-C, and CX 3 C chemokines, with C-C and C-X-C as the largest families [12,29] . Chemokines can be further classified as homeostatic and inflammatory chemokines, depending on whether they play a role in basal homeostatic immune-cell trafficking or in inflammation.…”

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confidence: 99%

Cellular Innate Immunity: An Old Game with New Players

et al. 2016

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Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.

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The Chemokine System in Innate Immunity

Cited by 655 publications

References 113 publications

Broad Infiltration of Macrophages Leads to a Proinflammatory State in Streptozotocin-Induced Hyperglycemic Mice

Broad Infiltration of Macrophages Leads to a Proinflammatory State in Streptozotocin-Induced Hyperglycemic Mice

Anti‐inflammatory effects of the GAG‐binding CXCL9(74‐103) peptide in dinitrofluorobenzene‐induced contact hypersensitivity in mice

Cellular Innate Immunity: An Old Game with New Players

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