Mapping the Immune Cell Microenvironment with Spatial Profiling in Muscle Tissue Injected with the Venom of Daboia...

Area of Science:

• Immunology
• Pathology
• Toxicology

Background:

• Muscle damage from snake venom exhibits regional and temporal variations in inflammatory responses.
• Understanding the immune cell microenvironment heterogeneity is crucial for studying venom-induced pathology.

Purpose of the Study:

• To investigate the immune cell microenvironment heterogeneity in a murine model of muscle necrosis induced by *Daboia russelii* venom.
• To correlate immune cell presence with the extent of muscle cell damage and time after venom injection.

Main Methods:

• Murine model of muscle necrosis induced by *Daboia russelii* venom.
• Histological and immunohistochemical analysis to assess muscle cell damage (desmin staining).
• GeoMx® Digital Spatial Profiler to quantify immune cell markers in damaged versus non-damaged muscle regions.

Main Results:

• A gradient of inflammatory cells (neutrophils, macrophages) was observed from necrotic to non-necrotic areas.
• Markers for monocytes, macrophages, dendritic cells, and neutrophils were elevated in damaged (low-desmin) regions, particularly at 24 hours post-injection.
• Apoptosis (BAD) and extracellular matrix (fibronectin) markers were also increased in damaged regions.

Conclusions:

• Snake venom-induced muscle injury displays significant immune cell microheterogeneity.
• The immune cell composition in venom-affected muscle is dependent on the degree of muscle cell damage and the time elapsed since envenomation.