Neutrophil-mediated inhibition of proinflammatory cytokine responses
| Autor: | Jos W. M. van der Meer, Mihai G. Netea, Frank L. van de Veerdonk, Mark S. Gresnigt, Charles A. Dinarello, Leo A. B. Joosten, Ineke Verschueren |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Proteases Neutrophils medicine.medical_treatment Phagocytosis Immunology Inflammation Biology Proinflammatory cytokine Invasive mycoses and compromised host [N4i 2] Mice Candida albicans medicine Immunology and Allergy Animals Humans Innate immune system Health aging / healthy living Pathogenesis and modulation of inflammation [IGMD 5] Candidiasis Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1] biology.organism_classification Pathogenesis and modulation of inflammation [N4i 1] Cytokine Neutrophil elastase biology.protein Cytokines Female medicine.symptom Inflammation Mediators Reactive Oxygen Species |
| Zdroj: | Journal of Immunology, 189, 4806-15 Journal of Immunology, 189, 10, pp. 4806-15 |
| ISSN: | 0022-1767 |
| Popis: | Neutrophils (polymorphonuclear neutrophils [PMNs]) play an elaborate role in the innate immune response against invading pathogens. Recent research provided evidence that PMNs can play a modulatory role in inflammation next to their primary role of phagocytosis. In the current study, we investigated whether neutrophils can modulate the innate immune response against Candida albicans. Production of the proinflammatory cytokines IL-1β and TNF-α by human PBMCs in response to C. albicans or LPS was decreased by coculture of PMNs; however, the anti-inflammatory cytokine IL-10 remained unaffected. Using Transwells and cells of patients with chronic granulomatous disease, we show that this downregulation of proinflammatory cytokine production was independent of phagocytosis and reactive oxygen species but was dependent on a soluble factor. We suggest that neutrophil-derived proteases are responsible for the downregulation of IL-1β and TNF-α, as cytokine production could be recovered by addition of α1-antitrypsin, an endogenous inhibitor of serine proteases. PMN lysates and neutrophil elastase could degrade recombinant human IL-1β and TNF-α but not IL-10, and this could be inhibited by addition of α1-antitrypsin. Moreover, we also provide evidence that the dampening effect of PMNs is present in vivo in a murine zymosan-induced arthritis model and a murine experimental endotoxemia model. Altogether, our data show that PMNs can dampen the proinflammatory response to C. albicans by protease-mediated degradation of cytokines. This observation suggest that PMNs might play a important regulatory role in the host defense against C. albicans and can be important for understanding the regulation of inflammation in general. |
| Databáze: | OpenAIRE |
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