Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase
| Autor: | Mihai G. Netea, Yock Young Dan, Winnie Leong, Raoul Herbrecht, Bart Jan Kullberg, Wee Joo Chng, Louis Yi Ann Chai, Sharada Ravikumar, Joan H. J. Lim, Jessamine Geraldine Goh, Mar Soe Win, Ai Ling Tan, Qiong Cao, Peter F. Troke |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neutropenia Neutrophils medicine.medical_treatment Immunology Interleukin-1beta lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Biology Microbiology Proinflammatory cytokine Immunomodulation 03 medical and health sciences Immune system All institutes and research themes of the Radboud University Medical Center Virology medicine Aspergillosis Humans Cells Cultured Peroxidase Microscopy Confocal Tumor Necrosis Factor-alpha medicine.disease 030104 developmental biology Cytokine lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Myeloperoxidase TLR4 biology.protein Tumor necrosis factor alpha Cell Adhesion Molecules Interferon regulatory factors |
| Zdroj: | Cellular Microbiology, 20, Cellular Microbiology, 20, 3, pp. |
| ISSN: | 1462-5814 |
| Popis: | Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus. |
| Databáze: | OpenAIRE |
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