Efferocytosis: A Potential Regulator of Cytokine Storm in Combating Hypervirulent Klebsiella pneumoniae Infection 9037
Year: 2025
Type: article
Abstract: Description Multidrug-resistant hypervirulent Klebsiella pneumoniae (hvKp) significantly threatens human health by causing a wide range of infections through the induction of cytokine storm. As impaired efferocytosis is a key factor in triggering pro-inflammatory response and the lack of studies focusing on promoting efferocytosis in hvKp infections, we hypothesize that profiling efferocytosis-related markers in neutrophils and macrophages may provide valuable therapeutic insights to treat hvKp infections. We found that hvKp infection impairs the efferocytosis of neutrophils by macrophages. This impairment correlates with decreased phosphatidylserine “eat me” signal and increased necrotic cell death markers expression in hvKp-infected neutrophils. Pro-inflammatory cytokine expression (Il6, Tnfa, and Il1b) was also higher in macrophages co-cultured with hvKp-infected neutrophils compared to uninfected neutrophils. Previous studies proved that miR-34a plays a vital role in inhibiting efferocytosis, and miR-34a inhibition alleviates proinflammatory response. Our preliminary study on RAW264.7 cells also identified miR-34a as a potential efferocytosis regulator and, we found that miR-34a antagomir treatment enhances efferocytosis of classical Kp-infected neutrophils by bone marrow-derived macrophages. Our study suggests an effective therapeutic strategy against the pathogenicity of hvKp infection by modulating miR-34a expression. Funding Sources RGC Theme-Based Research Scheme (T11-104/22-R) Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416446553
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