Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic...

Area of Science:

• Immunology
• Virology
• Metabolic disease

Background:

• Obesity impairs host immunity, leading to severe outcomes in various infections, including arthritogenic alphaviruses.
• The specific immune cell alterations in obesity during alphavirus infection are not well understood.

Purpose of the Study:

• To investigate the impact of obesity on immune cell responses during Mayaro virus (MAYV) infection using single-cell RNA sequencing.
• To compare immune cell landscapes in lean versus obese mice following MAYV infection.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of blood and tissue immune cells.
• Mayaro virus (MAYV) infection model in lean and obese mice.
• Analysis of gene expression related to immune responses and pathways.

Main Results:

• MAYV infection induced significant immune cell population shifts and upregulated interferon and inflammatory genes in both lean and obese mice.
• Lean mice exhibited a distinct macrophage subset with high interferon response gene expression in infected tissue, absent in obese mice.
• This unique macrophage population correlated with reduced inflammation severity in lean mice.

Conclusions:

• A specific macrophage subset in lean mice may enhance control of arthritogenic alphavirus infections.
• Obesity may impair this protective immune response, contributing to worse disease outcomes.
• These findings highlight the role of obesity in modulating immune cell function during viral infections.