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Multi‑omics reveal neutrophil heterogeneity in sepsis (Review)

  • Authors:
    • Zhi-Qiang Lin
    • Deng Chen
    • Pei-Dong Zhang
    • Jia-Liu Luo
    • Shun-Yao Chen
    • Shuai-Peng Gu
    • Yu-Jie Chen
    • You-Xie Shen
    • Ting-Xuan Tang
    • Te-Ding Chang
    • Li-Ming Dong
    • Cong Zhang
    • Zhao-Hui Tang
  • View Affiliations / Copyright

    Affiliations: Department of Trauma Surgery, Emergency Surgery and Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Trauma Surgery, Emergency Surgery and Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. Chin
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 222
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    Published online on: October 14, 2025
       https://doi.org/10.3892/ijmm.2025.5663
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Abstract

Sepsis is a life‑threatening disease characterized by a dysregulated immune response, and neutrophils serve an important role in pathogen clearance, multiple organ failure and immune regulation. With the discovery of multiple phenotypical and functional variants of neutrophils in sepsis, the heterogeneity of neutrophils is crucial, as it impacts the effectiveness of the immune response and the overall outcome of sepsis. Various genome, transcriptome, proteome and metabolome properties may contribute to this heterogeneity. Multi‑omics approaches unveil complex details of neutrophil behavior in the context of sepsis, highlighting how neutrophil phenotypes are differentially recruited and activated in response to various stimuli. The present review aimed to provide an overview of the differences in neutrophil phenotypes and functions during sepsis, focusing on neutrophil heterogeneity identified via multi‑omics methods. Comprehensive understanding of multi‑omics data regarding neutrophil heterogeneity enhances the diagnostic accuracy of sepsis and provides a scientific basis for individualized treatment strategies, potentially improving patient outcomes by targeting specific neutrophil functions and states.
View Figures

Figure 1

Phenotypical heterogeneity of
neutrophils in homeostasis and sepsis. Under homeostatic
conditions, immature neutrophils are characterized by expression of
CD64, CD49d and CXCR4, whereas mature neutrophils typically express
CD10, CD16b and CD35. During sepsis, both immature and mature
neutrophils are exposed to inflammatory cues that reprogram
cellular activities and functional states, leading to marked
phenotypical shifts. Specifically, surface molecules such as CD11b,
CD64, CD177, ICAM-1 and TREM-1 are upregulated, while CD10, CD62L,
CD16 and CXCR2 are downregulated. These alterations reflect changes
in neutrophil activation, adhesion and migration, however, the
precise functional consequences and regulatory mechanisms
underlying these transitions remain incompletely understood. CXCR,
C-X-C chemokine receptor; ICAM-1, intercellular adhesion
molecule-1; TREM-1, triggering receptor expressed on myeloid
cells-1.

Figure 2

Multi-omics approaches reveal
neutrophil heterogeneity and clinical implications in sepsis. Omics
layers include genome, transcriptome, proteome, metabolome and
microbiome. Neutrophil subsets and characteristics are identified
through single-omics studies and multi-omics integration in sepsis.
Potential clinical applications of neutrophil heterogeneity
profiling include early detection, patient stratification, targeted
therapy, prognostic modeling and precision medicine. eQTL,
expression quantitative trait loci; MPO, myeloperoxidase; H3K4me3,
histone H3 lysine 4 trimethylation; PI3K/AKT, phosphatidylinositol
3-kinase/protein kinase B; PD-L1, programmed death-ligand 1; MKI67,
marker of proliferation Ki-67; CYP1B1, cytochrome P450 family 1
subfamily B member 1; CEACAM8, carcinoembryonic antigen-related
cell adhesion molecule 8; S100A8/9, S100 calcium-binding protein
A8/9; LDHA, lactate dehydrogenase A; Neu1, neutrophil subtype
1.
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Copy and paste a formatted citation
Spandidos Publications style
Lin Z, Chen D, Zhang P, Luo J, Chen S, Gu S, Chen Y, Shen Y, Tang T, Chang T, Chang T, et al: Multi‑omics reveal neutrophil heterogeneity in sepsis (Review). Int J Mol Med 56: 222, 2025.
APA
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S. ... Tang, Z. (2025). Multi‑omics reveal neutrophil heterogeneity in sepsis (Review). International Journal of Molecular Medicine, 56, 222. https://doi.org/10.3892/ijmm.2025.5663
MLA
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S., Chen, Y., Shen, Y., Tang, T., Chang, T., Dong, L., Zhang, C., Tang, Z."Multi‑omics reveal neutrophil heterogeneity in sepsis (Review)". International Journal of Molecular Medicine 56.6 (2025): 222.
Chicago
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S., Chen, Y., Shen, Y., Tang, T., Chang, T., Dong, L., Zhang, C., Tang, Z."Multi‑omics reveal neutrophil heterogeneity in sepsis (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 222. https://doi.org/10.3892/ijmm.2025.5663
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Z, Chen D, Zhang P, Luo J, Chen S, Gu S, Chen Y, Shen Y, Tang T, Chang T, Chang T, et al: Multi‑omics reveal neutrophil heterogeneity in sepsis (Review). Int J Mol Med 56: 222, 2025.
APA
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S. ... Tang, Z. (2025). Multi‑omics reveal neutrophil heterogeneity in sepsis (Review). International Journal of Molecular Medicine, 56, 222. https://doi.org/10.3892/ijmm.2025.5663
MLA
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S., Chen, Y., Shen, Y., Tang, T., Chang, T., Dong, L., Zhang, C., Tang, Z."Multi‑omics reveal neutrophil heterogeneity in sepsis (Review)". International Journal of Molecular Medicine 56.6 (2025): 222.
Chicago
Lin, Z., Chen, D., Zhang, P., Luo, J., Chen, S., Gu, S., Chen, Y., Shen, Y., Tang, T., Chang, T., Dong, L., Zhang, C., Tang, Z."Multi‑omics reveal neutrophil heterogeneity in sepsis (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 222. https://doi.org/10.3892/ijmm.2025.5663
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