Infections can lead to a variety of symptoms, and one common indication is the loss of fat and muscle, known as wasting. Researchers at Salk Institute, led by Professor Janelle Ayres, investigated whether wasting could serve a beneficial purpose in battling infections.
The study, published in Cell Reports on July 24, 2023, focused on T brucei infection in mice. The researchers discovered that the wasting response to this infection occurs in two phases, each regulated by different immune cells. While fat loss did not benefit the fight against the infection, muscle loss did, suggesting that some forms of wasting may actually help manage illness.
“We often make assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates,” states senior author Ayres, Salk Institute Legacy Chair and head of the Molecular and Systems Physiology Laboratory. “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.”
The immune response against an invader demands a significant amount of energy, and prior studies suggested that this energy consumption led to wasting. However, Ayres and her team wanted to determine if wasting could have potential benefits rather than being solely a side effect.
The researchers focused on specialized immune cells called CD4+ and CD8+ T cells, which play crucial roles in fighting infections. They hypothesized that these T cells might be responsible for wasting and that wasting might be a cooperative effort between the two cell types.
“Our discoveries were so surprising that there were times I wondered if we did something wrong,” states first author Samuel Redford, a current visiting researcher and former graduate student in Ayres’ lab. “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.”
To study the relationship between CD4+ and CD8+ T cells and wasting, the team utilized the parasite T brucei, which lives in fat and can block the adaptive immune response, including T cell activity.
The findings revealed that CD4+ T cells were responsible for initiating fat wasting, while CD8+ T cells independently initiated muscle wasting. Surprisingly, CD4+ T cell-induced fat wasting had no impact on the mice’s ability to fight the T brucei infection or survive it. On the other hand, CD8+ T cell-induced muscle wasting, contrary to traditional assumptions about wasting, actually helped the mice fight the infection and survive.
“We can learn so much about our immune systems by looking at the environments and infections we have co-evolved with,” speaks Ayres. “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.”
This study highlights the significant role of immune cells in both fat and muscle wasting and emphasizes the need to understand the functions of such responses to inform therapeutic interventions. By gaining a better understanding of wasting, researchers hope to develop more effective treatments that can spare individuals from wasting and improve their chances of survival and recovery across various infections, cancers, and chronic illnesses.
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