Wasting, the simultaneous loss of fat and muscle, has long been observed as a common symptom during infections. Seeking to unravel the potential benefits of this process in fighting infections, scientists at the Salk Institute, led by Professor Janelle Ayres, conducted an innovative study using mice infected with the parasite T. brucei. Their findings, published in Cell Reports on July 24, 2023, challenge conventional beliefs about wasting and provide crucial insights into its underlying mechanisms.
This research marks a significant step forward in our understanding of wasting during infections, challenging preconceived notions about its significance and implications. By identifying the specific immune cells responsible for fat and muscle loss, the study has the potential to pave the way for targeted therapies that spare patients from wasting and enhance their ability to combat infections and other related diseases.
The study revealed that wasting during T. brucei infection occurs in two distinct phases, each governed by different types of immune cells. The researchers focused on two specialized T cell types, CD4+ and CD8+, which are known to play key roles in the immune response.
To investigate the relationship between these T cell types and wasting, the team used the parasite T. brucei as it resides in fat and can hinder the adaptive immune response, making it an ideal model to study fat wasting and T cell involvement.
Their findings demonstrated that CD4+ T cells are responsible for initiating the process of fat wasting. Surprisingly, the fat loss induced by CD4+ T cells had no impact on the mice's ability to fight the T. brucei infection or their survival. However, independently of the fat wasting process, CD8+ T cells were found to trigger muscle wasting. In a surprising twist, this muscle loss was found to enhance the mice's ability to fight the infection and survive.
Senior author Janelle Ayres, the Salk Institute Legacy Chair and head of the Molecular and Systems Physiology Laboratory, commented on the unexpected results, "We often make assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates. 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 study not only provides new insights into the role of immune cells in fat and muscle wasting during infection but also offers valuable information for developing more effective therapeutics that can spare individuals from wasting. Moreover, it has the potential to improve our understanding of wasting's impact on survival and morbidity in various diseases, such as infections, cancers, and chronic illnesses.
First author Samuel Redford, a current visiting researcher and former graduate student in Ayres' lab, expressed his astonishment at the results, saying, "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."
This groundbreaking research highlights the importance of studying immune cells in both fat and muscle wasting and emphasizes the need to understand the underlying mechanisms to develop effective therapeutic interventions. As the team extrapolates their findings to other diseases involving immune-mediated wasting, the study opens up promising avenues for novel treatments and potential breakthroughs in managing a wide range of illnesses.