Chinese Researchers Identify Spleen-to-Lung Immune Axis Critical for Antiviral Defense in SARS-CoV-2 Models

New research identifies the spleen as a critical source of neutrophils during lung infections, revealing a coordinated inter-organ network for antiviral response.

By: AXL Media

Published: Mar 24, 2026, 4:48 AM EDT

Source: Information for this report was sourced from Chinese Academy of Medical Sciences

Redefining the Origins of Pulmonary Inflammation

For years, the medical community has debated the precise origins of the massive neutrophil infiltration that characterizes severe respiratory viral infections. Traditional models suggested these white blood cells were either residents of the lung or recruited exclusively from bone marrow. However, new research from the Chinese Academy of Medical Sciences, published in the journal Immunity & Inflammation, identifies a dynamic spleen-to-lung neutrophil axis. Using a golden hamster model of SARS-CoV-2, the team discovered that at the height of an infection, the spleen functions as a strategic hub, mobilizing a continuous stream of neutrophils to the lungs. This inter-organ crosstalk suggests that the body’s innate immune defense is far more coordinated across different organs than previously understood.

The Role of Single-Cell RNA Velocity in Tracking Immune Cells

To map this complex cellular movement, the research team utilized advanced single-cell RNA velocity analysis, which allowed them to predict the future state of individual cells based on their current gene expression. At seven days post-infection, they identified a unidirectional trajectory where neutrophils moved from a proliferating stage to a fully activated state. The analysis revealed that local lung cell proliferation was insufficient to account for the total number of immune cells present during the peak of the antiviral response. According to the study, this transcriptomic "gap" pointed toward an external source of cells, leading researchers to investigate the synchronized spike in neutrophil activity occurring simultaneously within the spleen.

Spatial Transcriptomics Confirms Splenic Seed Cells

The researchers employed spatial transcriptomics and the Redeconve algorithm to pinpoint the exact location and origin of these immune cells within the pulmonary architecture. The results were definitive: among all immune cell types analyzed, only neutrophils showed a massive contribution from splenic sources. By the one-week mark following infection, the proportion of spleen-derived neutrophils in the lung actually rivaled or exceeded those that were locally derived. This finding confirms that the spleen does not just store these cells but actively seeds the lung with a diverse population of neutrophils at various stages of differentiation, from...