Although infections can present with many different symptoms, one common symptom is the loss of fat and muscle, a process called wasting. Salk scientists wanted to know whether wasting was beneficial in fighting infections.
Researchers in Professor Janelle Ayres' lab discovered the wasting response to T. brucei infection in mice occurs in two phases, each regulated by different immune cells. While fat loss did not benefit the fight against infection, muscle loss did -- a surprising clue that some wasting may help manage illness.
The findings, published in Cell Reports on July 24, 2023, can inform the development of more effective therapeutics that spare people from wasting and increase our understanding of how wasting influences survival and morbidity across infections, cancers, chronic illnesses, and more.
"We oftenmake assumptions that conditions like wasting are bad, since they often coincide with higher mortality rates," says 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."
Defending the body from an invader requires a lot of energy. Prior studies suggested this immune-related energy consumption had the unfortunate consequence of wasting. But Ayres and team were curious to know whether wasting could be beneficial and not just a side effect.
Specialized immune cells called T cells are slow to respond to infections, but when they do respond, they adapt to fight the particular infection. Ayres was interested to know whether it was these T cells causing wasting. If T cells are responsible for the condition, that would indicate wasting is not simply an unproductive side effect of energy-hungry immune cells.
The cells of interest are called CD4+ and CD8+ T cells. CD4+ T cells lead the fight against infection and can promote the activity of CD8+ T cells, which can kill invaders and cancerous cells. The two T cell types often work together, so the researchers hypothesized their role in wasting may be a cooperative effort, too.
To work out the relationship between CD4+ and CD8+ T cells and wasting, the researchers turned to the parasite T. brucei. Because T. brucei lives in fat and can block the adaptive immune response -- which includes T cells -- it was a perfect model infection for their questions about fat wasting and how T cells mediate that process.
The team investigated 1) the role of CD4+ and CD8+ T cells during T. brucei infection and 2) how removing CD4+ and CD8+ T cells changed the longevity, mortality rates, parasite symptoms, and amount of parasite present in infected mice.
The researchers found that CD4+ T cells acted first and initiated the process of fat wasting. Afterward, but completely independently of the fat wasting, CD8+ T cells initiated the process of muscle wasting. The CD4+ T cell-induced fat wasting had no impact on the ability for the mice to fight T. brucei or to survive infection. The CD8+ T cell-induced muscle wasting, however, contrary to the traditional assumptions about wasting, helped the mice fight T. brucei and survive the infection.
"Our discoveries were so surprising that there were times I wondered if we did something wrong," says 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."
The findings illustrate the important role of immune cells in both fat and muscle wasting and the necessity to understand the function of such responses to inform therapeutic interventions.
"We can learn so much about our immune systems by looking at the environments and infections we have co-evolved with," says 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."
In the future, the team will examine the T cell mechanism in other mammals and eventually humans. They also want to explore in more detail why muscle wasting is occurring and why CD4+ and CD8+ T cells play these distinct roles.
Other authors include Siva Karthik Varanasi, Karina Sanchez, and Natalia Thorup of Salk.
The work was supported by the National Institutes of Health (DPI AI144249, R01AI14929, NCI CCSG: P30 CA014195).
FAQs
The findings revealed that CD4+ T cells took the lead and triggered the process of fat wasting. Subsequently, but independently from fat wasting, CD8+ T cells initiated muscle wasting.
Why do infections cause weight loss? ›
Serious infections, for example, TB and HIV, and inflammatory conditions, such as rheumatoid arthritis, also raise your metabolic rate and induce weight loss. Your doctor can assess your symptoms and check your blood for markers of infection and inflammation to rule out infective or inflammatory causes of weight loss.
Does infection cause muscle loss? ›
LA JOLLA—Although infections can present with many different symptoms, one common symptom is the loss of fat and muscle, a process called wasting.
Why do we lose muscle when sick? ›
During critical illness, factors such as immobilisation and altered neuroendocrine responses cause muscle wasting by making protein balance negative [8].
Does your body burn fat or muscle when sick? ›
These chemicals are called cytokines and contribute to the loss of fat and muscle. The chemicals may make your metabolism speed up so that you use up calories faster. Because your body is using up energy faster than it is getting it, you can have severe weight loss. This can happen even if you are eating normally.
Why do people lose so much weight when sick? ›
"Most of that weight loss is dehydration." If you're able to compensate for all the fluids you're losing by drinking enough, you shouldn't lose more than a few pounds, Dr. Beuther says.
Can bad bacteria cause weight loss? ›
Scientists have found that specific gut bugs and the balance between different types of bugs may influence how easily a person can manage their weight. ZOE research has linked many of the “good” gut bugs we've identified to lower weight and less belly fat and some of the “bad” bugs to increased weight and belly fat.
What happens when your body is fighting an infection? ›
White blood cells, antibodies, and other mechanisms go to work to rid your body of the foreign invader. Indeed, many of the symptoms that make a person suffer during an infection—fever, malaise, headache, rash—result from the activities of the immune system trying to eliminate the infection from the body.
What infection attacks the muscles? ›
Viral infections are the most common infections causing myositis. Rarely, bacteria, fungi, or other organisms can cause myositis as well. Viruses or bacteria may invade muscle tissue directly, or release substances that damage muscle fibers.
Can a bacterial infection affect your muscles? ›
What is pyomyositis? Pyomyositis (sometimes called tropical pyomyositis) is a rare and treatable bacterial infection that affects skeletal muscles (the muscles you use to move). Pyomyositis usually results in an abscess (a swollen area that contains pus) that forms in your muscle.
"If your symptoms are above the neck, including a sore throat, nasal congestion, sneezing, and tearing eyes, then it's OK to exercise," he says. "If your symptoms are below the neck, such as coughing, body aches, fever, and fatigue, then it's time to hang up the running shoes until these symptoms subside."
How do you reduce muscle loss when sick? ›
A recent report published in the Biochemistry Journal found that decreased levels of water resulted in cell shrinking, which causes muscle protein breakdown. Drinking plenty of fluids will help stop this from happening and even promote protein synthesis.
Why do muscles look smaller when sick? ›
Many factors contribute to muscle loss - lack of physical activity, poor nutrition, illness or injury, genetics, and various medical conditions. When muscles are not being used, our bodies can break down the tissue to conserve energy, causing muscle fibers to shrink and appear smaller.
Do you lose weight when fighting an infection? ›
Salk scientists discover role immune system's T cells play in regulating fat and muscle loss during infection in mice. Newswise — LA JOLLA (July 24, 2023)—Infections can manifest in various ways, but a prevalent symptom is the depletion of fat and muscle, known as wasting.
Can infection cause weight loss? ›
It would be unusual not to have other symptoms with a chronic infection. But, occasionally, the first symptom that is noticed with infections such as tuberculosis or HIV is weight loss. Hookworm infection of the gut is another example where weight loss may be the first indication of disease.
Why do I weigh more when I'm sick? ›
Illness and disease can bring unexpected weight change. Cancer, diabetes, heart failure, and even the common cold can have ripple effects. If you lose your appetite or retain water, that may tip the scale one way or the other. Talk with your doctor if you see changes that you didn't expect.
Do you lose weight fighting an infection? ›
brucei infection in mice. This response occurs in two distinct phases, each controlled by different immune cells. Surprisingly, while the loss of fat did not contribute to the fight against infection, the loss of muscle did. This finding suggests that certain types of wasting might actually aid in managing illness.
What is the most common cause of unexplained weight loss? ›
Losing weight without trying may indicate an underlying condition. Conditions that cause unexplained weight loss include overactive thyroid, inflammatory bowel disease, and depression. A good rule of thumb is to see your doctor if you've lost a significant amount — more than 5% of your weight — within 6 to 12 months.
Can a blood infection cause weight loss? ›
Many septic survivors experience severe weakness, weight loss, muscle loss, and functional decline upon discharge (16). Survival from sepsis remains challenging, and survivors often require long hospital stays and suffer from frailty and long-term morbidity.
