CD8⁺ T cells induce cachexia during chronic viral infection

Area of Science:

• Immunology
• Pathophysiology
• Metabolic Diseases

Background:

• Cachexia, a complex metabolic syndrome, significantly increases morbidity and mortality in cancer, chronic inflammation, and infections.
• The specific mechanisms underlying infection-associated cachexia (IAC) remain poorly understood.
• Existing research primarily focuses on cancer-associated cachexia, leaving a gap in understanding IAC.

Purpose of the Study:

• To elucidate the mechanisms driving infection-associated cachexia (IAC).
• To investigate the role of CD8+ T cells in IAC using a mouse model.
• To differentiate IAC mechanisms from those of cancer-associated cachexia.

Main Methods:

• Development of a reversible cachexia model in mice with chronic viral infection.
• Analysis of adipose tissue morphology and molecular changes.
• Assessment of CD8+ T cell responses, type I interferon signaling, and antigen-specific priming.

Main Results:

• Virus-specific CD8+ T cells, not cancer-associated cachexia cytokines, were identified as key drivers of IAC.
• CD8+ T cells induced significant morphologic and molecular alterations in adipose tissue, leading to lipid store depletion.
• These adipose tissue changes occurred prior to the peak CD8+ T cell response and were dependent on T cell-intrinsic type I interferon signaling and antigen priming.

Conclusions:

• Systemic antiviral immune responses are directly linked to adipose tissue remodeling in IAC.
• CD8+ T cells play a critical, previously underappreciated role in the pathogenesis of infection-associated cachexia.
• Understanding these CD8+ T cell-mediated mechanisms opens new avenues for therapeutic interventions in IAC.