Interleukin-17A released from intestinal γδT cells induces cytokine storm in mice with severe dengue
Year: 2022
Type: preprint
Abstract: Blockade of TNF-α signaling protects mice from lethal infection with dengue virus (DENV); however, what causes cytokine storm or how TNF-α aggravates the disease remains unknown. Here, we performed transcriptome analysis of the liver and small intestine samples collected chronologically from DENV-3 P12/08-infected IFN-α/β and γ receptor knockout (IFN-α/β/γRKO) mice in the presence/absence of blockade of TNF-α Ab signaling. We found that TNF-α induced production of IL-17A by small intestinal γδT cells, regulated production of other cytokines such as IL-6 cooperatively with TNF-α, and played a crucial role in mortality. Also, neutrophil-derived matrix metalloprotease-8 was identified as an effector molecule causing vascular leakage. Blockade of TNF-α or IL-17A signaling strongly inhibited nuclear translocation of NF-κB p65 in stroma-like cells and epithelial cells, and prevented induction of IL-6. These findings enable us to better understand cytokine storm associated with severe dengue, and may facilitate development of new therapeutic strategies.
Source: Research Square
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1070351364, Analysis of severe disease mechanism using mouse model infected with dengue virus, developing the symptoms of vascular leakage and bone marrow suppression., Complete elucidation of pathogenic mechanism of severe dengue in mouse model, developing the symptoms of vascular leakage induced by cytokine storm., G7475120045
OpenAlex ID: W4296080854