Pulmonary megakaryocytes orchestrate host defense via PcrV-induced NF-κB signaling in Pseudomonas aeruginosa infection
4 affiliations
- 1Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, Chongqing, 400037 China
- 2Laboratory Medicine Department, Zigong Fourth People’s Hospital, Sichuan, 643000 China
- 3Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, Chongqing, 400037 China
- 4School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030 China
Abstract
Background: Megakaryocytes, beyond their classical role in platelet formation, are increasingly recognized as immune modulators. This study aimed to investigate the function and activation mechanisms of megakaryocytes during Pseudomonas aeruginosa (PA) infection, focusing on their interaction with bacterial toxins and innate immune pathways.
Methods: This study evaluated the response of pulmonary megakaryocytes to PA-induced acute pneumonia in mice. Specifically, the activation status of pulmonary megakaryocytes was determined by flow cytometry and sorting, followed by RNA sequencing, combining Gene Ontology and Gene Set Enrichment Analysis. The expression of pro-inflammatory cytokines and chemokines within megakaryocytes after PA infection were detected by qPCR and fluorescent confocal imaging. The effect of megakaryocytes on the chemotaxis and recruitment of neutrophils and monocytes was demonstrated using chemotaxis assays. Additionally, purified PA toxins were injected into the lungs of mice in vivo or added to flow-sorted cells in vitro in order to induce inflammation and evaluate the response of megakaryocytes to a single PA toxin. The activation status of intracellular signaling pathways was verified through inhibitor-mediated blocking experiments.
Results: PA infection significantly activates megakaryocytes, which promote the recruitment of phagocytes and enhance the host’s defense against PA infection. The innate immune response in the lungs was diminished during the early stages of PA infection among the megakaryocytes depleted mice, resulting in increased bacterial load and higher mortality. Flow cytometry sorting followed by RNA sequencing indicated that megakaryocytes exhibit a typical pro-inflammatory phenotype, along with NF-κB pathways activation. Furthermore, the PA toxin PcrV was identified as a key NF-κB activator on megakaryocytes, as demonstrated by increased expression of inflammatory markers and chemokines in response to PcrV. Inhibition of NF-κB signaling attenuated this pro-inflammatory phenotype of megakaryocytes.
Conclusions: This study provides new insights into how megakaryocytes shape the cytokine and chemokine landscape in the lung during PA infection. It highlights the intrinsic interactions between megakaryocytes and phagocytes during pathogen invasion, suggests that managing megakaryocyte activity could be a new strategy to enhance immune defense.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03072-y.
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BibTeX
@article{guo2026pulmonary,
title = {{Pulmonary megakaryocytes orchestrate host defense via PcrV-induced NF-κB signaling in Pseudomonas aeruginosa infection}},
author = {Xiaolong Guo and Qian Dai and Xiping Liao and Yannan Ma and Hengqian Liu and Junzhi Xiong and Hua Yu and Yuanyuan Li and Kebin Zhang and Jianyun Zhou and Hongli Zhou},
journal = {Cell Communication and Signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03072-y},
url = {https://doi.org/10.1186/s12964-026-03072-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pulmonary megakaryocytes orchestrate host defense via PcrV-induced NF-κB signaling in Pseudomonas aeruginosa infection
AU - Xiaolong Guo
AU - Qian Dai
AU - Xiping Liao
AU - Yannan Ma
AU - Hengqian Liu
AU - Junzhi Xiong
AU - Hua Yu
AU - Yuanyuan Li
AU - Kebin Zhang
AU - Jianyun Zhou
AU - Hongli Zhou
PY - 2026
DA - 2026/07/01
JO - Cell Communication and Signaling : CCS
DO - 10.1186/s12964-026-03072-y
UR - https://doi.org/10.1186/s12964-026-03072-y
AB - Background: Megakaryocytes, beyond their classical role in platelet formation, are increasingly recognized as immune modulators. This study aimed to investigate the function and activation mechanisms of megakaryocytes during Pseudomonas aeruginosa (PA) infection, focusing on their interaction with bacterial toxins and innate immune pathways. Methods: This study evaluated the response of pulmonary megakaryocytes to PA-induced acute pneumonia in mice. Specifically, the activation status of pulmonary megakaryocytes was determined by flow cytometry and sorting, followed by RNA sequencing, combining Gene Ontology and Gene Set Enrichment Analysis. The expression of pro-inflammatory cytokines and chemokines within megakaryocytes after PA infection were detected by qPCR and fluorescent confocal imaging. The effect of megakaryocytes on the chemotaxis and recruitment of neutrophils and monocytes was demonstrated using chemotaxis assays. Additionally, purified PA toxins were injected into the lungs of mice in vivo or added to flow-sorted cells in vitro in order to induce inflammation and evaluate the response of megakaryocytes to a single PA toxin. The activation status of intracellular signaling pathways was verified through inhibitor-mediated blocking experiments. Results: PA infection significantly activates megakaryocytes, which promote the recruitment of phagocytes and enhance the host’s defense against PA infection. The innate immune response in the lungs was diminished during the early stages of PA infection among the megakaryocytes depleted mice, resulting in increased bacterial load and higher mortality. Flow cytometry sorting followed by RNA sequencing indicated that megakaryocytes exhibit a typical pro-inflammatory phenotype, along with NF-κB pathways activation. Furthermore, the PA toxin PcrV was identified as a key NF-κB activator on megakaryocytes, as demonstrated by increased expression of inflammatory markers and chemokines in response to PcrV. Inhibition of NF-κB signaling attenuated this pro-inflammatory phenotype of megakaryocytes. Conclusions: This study provides new insights into how megakaryocytes shape the cytokine and chemokine landscape in the lung during PA infection. It highlights the intrinsic interactions between megakaryocytes and phagocytes during pathogen invasion, suggests that managing megakaryocyte activity could be a new strategy to enhance immune defense. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12964-026-03072-y.
SN - 1478-811X
ER -