Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase.

Abstract

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.

• Authors: Jessamine G Goh, Sharada Ravikumar, Mar Soe Win, Qiong Cao, Ai Ling Tan, Joan H J Lim, Winnie Leong, Raoul Herbrecht, Peter F Troke, Bart Jan Kullberg, Mihai G Netea, Wee Joo Chng, Yock Young Dan, Louis Y A Chai
• Journal: Cellular microbiology (Cell Microbiol) Vol. 20 Issue 3 (03 2018) ISSN: 1462-5822 [Electronic] India
• PMID: 29088499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Cell Adhesion Molecules
• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• Peroxidase

Topics

• Aspergillosis (immunology)
• Cell Adhesion Molecules (metabolism)
• Cells, Cultured
• Humans
• Immunomodulation (immunology, physiology)
• Interleukin-1beta (metabolism)
• Microscopy, Confocal
• Neutropenia (immunology, metabolism)
• Neutrophils (immunology, metabolism, physiology)
• Peroxidase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)