RT Journal Article
SR Electronic
T1 Cytokine storm and vascular leakage in severe dengue: insights from single-cell RNA profiling
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202403008
DO 10.26508/lsa.202403008
VO 8
IS 6
A1 Al Kadi, Mohamad
A1 Yamashita, Maika
A1 Shimojima, Masayuki
A1 Yoshikawa, Tomoki
A1 Ebihara, Hideki
A1 Okuzaki, Daisuke
A1 Kurosu, Takeshi
YR 2025
UL http://www.life-science-alliance.org/content/8/6/e202403008.abstract
AB Severe dengue is characterized by vascular leakage triggered by a hyperinflammatory response, though the underlying mechanisms remain unclear. Our previous mouse model study highlighted the importance of small intestine in severe disease and identified key cytokines (IL-17A, TNF-α, and IL-6) involved. Here, we used a Fixed RNA Profiling assay to characterize key cytokine- and effector-producing cells, along with their receptor expression. Type 3 innate lymphoid cells (ILC3), Th17 cells, and γδ T cells emerged as pathologically relevant IL-17A/F-producing cells. These cells expressed IL-1β and IL-23 receptors, underscoring the significance of these signaling pathways. IL-1β was produced by M2-like macrophages, dendritic cells, and neutrophils, whereas M1-like macrophages, which differentiated post-infection, produced IL-23, TNF-α, and IL-6, acting as initiators and amplifiers of the cytokine storm. Newly differentiated neutrophils produced IL-1β and effector molecule matrix metalloprotease-8, suggesting a dual role in exacerbating the cytokine storm and directly mediating vascular leakage. Identified macrophages and neutrophils exhibited atypical characteristics. These findings provide new pathological insights into severe dengue and broader mechanism underlying cytokine storm-related diseases.The single-cell analysis data of the mouse small intestine reported in this study were deposited in the Sequence Read Archive (SRA) under the accession number: PRJNA1138486.