Comparative RNA-Seq Analysis Reveals Macrophage Polarization and T Cell Exhaustion Signatures in Visceral...

Area of Science:

• Immunology
• Genomics
• Parasitology

Background:

• Syrian golden hamsters (Mesocricetus auratus) are a key model for visceral leishmaniasis (VL) pathology.
• Mice (Mus musculus, BALB/c) are used for pharmaceutical and immunological response evaluation.
• Understanding species-specific gene signatures is crucial for VL research.

Purpose of the Study:

• To precisely define the role of gene signatures in L. donovani-infected M. auratus and M. musculus.
• To compare transcriptomic profiles and identify common and distinct molecular responses.
• To elucidate immunological mechanisms driving VL pathogenesis in rodent models.

Main Methods:

• Transcriptomic analysis of spleen samples from infected and uninfected M. auratus and M. musculus.
• Differential gene expression analysis to identify significant molecular changes.
• Principal component analysis (PCA) for distinct sample clustering.

Main Results:

• Distinct clustering observed between uninfected and infected groups in both species.
• 2054 genes differentially expressed in M. auratus, 1108 in M. musculus; 153 common.
• Overexpression of LAG3 in both species indicates T cell exhaustion; IL-10 overexpression unique to M. musculus.

Conclusions:

• Both hamster and mouse models exhibit Th1-mediated immune signaling and T cell exhaustion.
• Species-specific immune responses and gene expression patterns influence VL pathogenesis.
• Genes like Tgm2, Clec7a, and Adora2b may play a significant role in disease outcome across both models.