New study explains why we lose fat and muscle during infections

Researchers have made a significant discovery concerning the involvement of T cells from the immune system in the regulation of fat and muscle loss during infections in mice.

Researchers at Professor Janelle Ayres’ lab have made a significant discovery regarding the wasting response to T. brucei infection in mice. The researchers found that this wasting response occurs in two distinct phases, each controlled by different immune cells. Surprisingly, they observed that while fat loss did not contribute to the fight against infection, muscle loss did, suggesting that certain types of wasting might actually aid in managing illness.

Published in Cell Reports on July 24, 2023, these findings have the potential to revolutionize the development of more effective therapeutics that can spare individuals from wasting. Additionally, they offer valuable insights into how wasting impacts survival and morbidity in various conditions, including infections, cancers, and chronic illnesses.

Senior author Ayres, who holds the Salk Institute Legacy Chair and leads the Molecular and Systems Physiology Laboratory, emphasizes the importance of questioning assumptions about conditions like wasting. While they are often associated with higher mortality rates, understanding the purpose of wasting can lead to unexpected and valuable answers about the human response to infections and how to optimize that response.

Previous studies had suggested that immune-related energy consumption during defending the body against invaders led to wasting as an unfortunate side effect. However, Ayres and her team’s research opens up the possibility that some forms of wasting might serve a beneficial purpose, challenging the conventional notion that all wasting is inherently harmful. This breakthrough could shed light on new avenues for enhancing our immune responses and developing targeted interventions for various health conditions.

Researchers conducted a study to understand the role of specialized immune cells called T cells in a condition known as wasting, where the body loses both fat and muscle mass during infections. Specifically, they focused on two types of T cells: CD4+ and CD8+ T cells. CD4+ T cells lead the immune response and can promote the activity of CD8+ T cells, which are responsible for killing invaders and cancerous cells.

To investigate the relationship between these T cells and wasting, the researchers used the parasite T. brucei, which can live in fat and block the adaptive immune response (including T cells). This parasite served as a model infection to study how T cells mediate wasting.

The study revealed that CD4+ T cells were responsible for initiating fat wasting, while CD8+ T cells independently triggered muscle wasting. Surprisingly, the fat wasting caused by CD4+ T cells did not affect the mice’s ability to fight T. brucei or survive the infection. On the other hand, the muscle wasting induced by CD8+ T cells actually helped the mice fight the parasite and survive the infection.

The findings challenged previous assumptions about wasting and highlighted the crucial role of immune cells in both fat and muscle wasting. Understanding these responses can lead to important insights for developing therapeutic interventions.

The researchers expressed their excitement about how studying infections like T. brucei can teach us about the human immune system and help us combat various diseases involving immune-mediated wasting, such as parasites, tumors, and chronic illnesses.

In the future, the team plans to explore the T cell mechanisms in other mammals, including humans. They also aim to investigate in more detail why muscle wasting occurs and why CD4+ and CD8+ T cells have distinct roles in this process. The research holds promise for advancing our understanding of immune responses and potential treatments for wasting-related conditions.

Source of Story :

Samuel E. Redford, Siva Karthik Varanasi, Karina K. Sanchez, Natalia R. Thorup, Janelle S. Ayres. CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection. Cell Reports, 2023; 112814 DOI: 10.1016/j.celrep.2023.112814

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