New study reveals what happens to fat and muscle during infection.

Researchers at Salk find that immune system T cells control the loss of muscle and fat in infected mice.

Although infections may cause a wide range of symptoms, wasting, or the loss of muscle and fat, is one typical sign. Scientists at Salk wanted to see whether wasting helped treat infections.

The team, working in Ayres’ lab, revealed that the response to a T. brucei infection in mice resulting in wasting takes place in two distinct stages, with each being controlled by diverse immune cells.

Interestingly, while fat loss didn’t improve the battle against the infection, muscle loss did, indicating that some forms of wasting could assist in disease management.

The study, published in Cell Reports on July 24, 2023, provides valuable insights for creating more efficient treatments that can prevent wasting, while broadening our comprehension of how wasting impacts survival and the rate of sickness across a spectrum of infections, cancers, chronic diseases, among others.

Does fat or muscle loss increase the risk of dying?

“We often make assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates,” notes Ayres, the senior author of the study. “But if instead we ask, what is the purpose of wasting? We can find surprising and insightful answers that can help us understand the human response to infection and how we can optimize that response.”

Fighting off invaders requires substantial energy from the body. Previous research indicated that this high energy consumption of the immune system resulted in wasting. Ayres and her team, however, questioned if this wasting might have a positive role rather than merely being a negative side effect.

The focus fell on specialized immune cells called T cells.

What is the role of T cells in fat and muscle loss during infection?

These cells are slow to react to infections, but once they do, they are well-adapted to tackle the specific infection. Ayres and her team hypothesized whether these T cells were the culprit behind wasting.

Their study centered around the CD4+ and CD8+ T cells. CD4+ T cells are the frontline soldiers in the battle against infection and can enhance the activity of CD8+ T cells, which are capable of eliminating invaders and cancerous cells.

Given that these T cell types often collaborate, the team explored the possibility of a joint effort in causing wasting.

The parasite T. brucei was the researchers’ target, as this parasite resides in fat and can impede the adaptive immune response, making it an excellent model for their queries about fat wasting and the role of T cells in this process.

Why does wasting occur during infection?

Through their investigations, the researchers discerned that CD4+ T cells were the initial triggers of fat wasting. However, independently of this process, CD8+ T cells instigated muscle wasting.

Importantly, the CD4+ T cell-induced fat wasting had no bearing on the ability of the mice to combat T. brucei or survive the infection.

Contrarily, CD8+ T cell-induced muscle wasting aided the mice in their fight against T. brucei, enhancing their survival.

Samuel Redford, the first author of the study, stated, “Our discoveries were so surprising that there were times I wondered if we did something wrong. We had striking results that mice with fully functioning immune systems and mice without CD4+ T cells lived the same amount of time—meaning, those CD4+ T cells and the fat wasting they caused were completely disposable in fighting the parasite. And beyond that, we found that normally cooperative T cell subtypes were working totally independently of one another.”

These findings underscore the vital role of immune cells in both fat and muscle wasting and highlight the need to understand these processes’ functions to inform the development of therapeutic interventions.

“We can learn so much about our immune systems by looking at the environments and infections we have co-evolved with,” Ayres points out. “While T. brucei is an interesting and important case, what is exciting is extrapolating our findings to understand, treat, and overcome any disease that involves immune-mediated wasting—parasites, tumors, chronic illnesses, and so much more.”

In the future, the team aims to explore the T cell mechanism in other mammals and ultimately in humans. They also plan to delve deeper into why muscle wasting occurs and why CD4+ and CD8+ T cells have these distinct roles.

Source: 10.1016/j.celrep.2023.112814

Image Credit: Shutterstock