Altered neutrophil responses to dengue virus serotype three: delayed apoptosis is regulated by stabilisation of Mcl-1

• Published in: Scientific reports Vol. 14; no. 1; pp. 18414 - 10
• Main Authors: Kamsom, Chatcharin, Edwards, Steven W., Thaosing, Jiraphon, Papalee, Saitharn, Pientong, Chamsai, Kurosu, Takeshi, Phanthanawiboon, Supranee
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/2504/223/1699; 631/326/596/1413; Adaptive immunity; Apoptosis; Bcl-x protein; Cell Survival; CXCR4 protein; Dengue - immunology; Dengue - virology; Dengue fever; Dengue Virus - physiology; Global health; Granulocyte-macrophage colony-stimulating factor; Humanities and Social Sciences; Humans; Leukocyte migration; Leukocytes (neutrophilic); Life span; Lymph nodes; Mcl-1 protein; Monocyte chemoattractant protein 1; multidisciplinary; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Public health; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Serogroup; Tumor necrosis factor-α; Vector-borne diseases; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-68642-x

Dengue is a global health concern, and the host-viral interactions that regulate disease severity are largely unknown. Detrimental effects of neutrophils in this disease have been reported, but the precise mechanisms and functional properties of dengue-activated neutrophils are not fully characterised. Here, we measured the effects of dengue virus serotype 3 (DV3) on neutrophil lifespan and functions. We show that DV3 extends neutrophil survival with a significant proportion of cells surviving for 72 h post-incubation. These effects on neutrophil survival were greater than those observed by adding GM-CSF and TNF-α alone, but these cytokines enhanced survival induced by the virus. Enhanced reactive oxygen species (ROS) generation was observed following incubation with DV3 activation and this ROS production was enhanced by co-incubation with priming agents. In addition, DV triggered the enhanced IL-8 expression by the majority of neutrophils and a low percentage of cells were activated to express MCP-1 (CCL2). A low number of neutrophils showed increased co-expression of the migratory markers, CCR7 and CXCR4 which could promote their migration towards lymph nodes. DV3 significantly upregulated the BCL-XL gene at 3, 12, and 24 h, and the Mcl-1 gene at 12 h, following treatment. We also show that DV3 induces the Mcl-1 protein stabilization similar to GM-CSF. This report sheds new light on the mechanisms by which neutrophils may contribute to the pathology of dengue disease via delayed apoptosis and generation of pro-inflammatory molecules, and raises the possibility that dengue-activated neutrophils may play a role in activating cells of adaptive immunity.