Cells (green) become infected with bacteria (red). Credit: Salk Institute
Worldwide, more than one million deaths occur each year from diarrheal diseases that lead to dehydration and malnutrition. Yet there is no vaccine to combat or prevent these diseases, which are caused by bacteria such as certain strains of E. coli. Instead, people with bacterial infections must rely on the body to employ one of two defense strategies: kill the invaders or harm the invaders but keep them close. If the body chooses to attack the bacteria, the disease can occur without the diarrhea, but the infection can still be transmitted – a process called asymptomatic carriage.
Now Salk scientists have discovered that combining specific diets with disease-causing bacteria can create long-lasting immunity in mice without the cost of developing disease, revealing a new potential vaccination strategy. Their findings, published in Scientific progress on June 23, 2023, paving the way for the development of new vaccines that could boost immunity for people with diarrhea and possibly other infections.
“We found that immunization against diarrheal infections is possible if we allow the bacteria to retain some of its disease-causing behavior,” says senior author Professor Janelle Ayres, Legacy Chair of the Salk Institute and head of the Molecular and Systems Physiology Laboratory. “This understanding could lead to the development of vaccines that can reduce symptoms and mortality and provide protection against future infections.”
In 2018, Ayres’ lab investigated how nutritional interventions can induce an asymptomatic infection, which Ayres calls a cooperative relationship between bacteria and host (the person or animal infected by the bacteria) where the host does not experience any symptoms. They found that an iron-rich diet allowed mice to survive a normally deadly bacterial infection without ever developing any signs of illness or disease.
The iron-rich diet increased unabsorbed sugar (glucose) in the mice’s intestines, which the bacteria could feast on. The excess sugar served as a “bribe” for the bacteria, keeping them full and incentivizing them not to attack the host.
This process caused a long-term asymptomatic infection with the bacteria, leading the researchers to believe that the adaptive immune system (cells and proteins that “remember” infections) may be involved.
“It has not been possible to elicit lasting immunity against bacteria such as C. rodentium or E. coli using established vaccination strategies. We wanted to find out what mechanism maintained this long-lasting immunity so that we could use that mechanism to develop a to create an impactful solution against these diarrheal diseases,” says first author Grischa Chen, a former postdoctoral researcher in Ayres’ laboratory.
The researchers investigated how the body suppresses infection symptoms, whether an infection without symptoms can create long-lasting immunity and whether that immunity is reproducible as a vaccination strategy.
The team compared mice on iron-rich and normal diets after a C. rodentium infection to see if the diet had an effect on a symptomless infection. Immediately after infection, mice fed an iron-rich diet had no symptoms, while mice fed a normal diet had symptoms. All mice were then put on a normal diet to see if the asymptomatic infection would persist.
Mice with a non-functional adaptive immune system (the immune system that “remembers”) previous infections, whether or not they had ever been on an iron-rich diet, were unable to maintain a cooperative relationship with the bacteria. While the iron-rich diet suppressed symptoms immediately after infection, the adaptive immune system was necessary for sustained cooperation. Importantly, the mice with a functional adaptive immune system had the disease without any symptoms, with lasting immunity, as demonstrated by survival after reinfection at one month.
Ayres and team concluded that only an iron-rich diet can prevent bacteria from causing deadly symptoms in mice during active infection. But a functional adaptive immune system is required for immunity against future infections in the absence of nutritional supplements.
Some strains of bacteria, if mutated enough, do not cause symptoms. To test whether such bacteria could produce lasting immunity, the team repeated their iron diet versus normal diet experiment in mice, but this time with bacteria that could cause disease and bacteria that couldn’t cause disease. They found that only mice fed disease-causing, non-mutated bacteria were able to sustain immunity upon re-infection.
The scientists note that people should not consume large amounts of iron after reading this study. Their findings are preliminary and will need to be confirmed in human subjects.
The researchers hope that their insights will provide a basis for future research in humans and the creation of a vaccine regiment that protects and prevents against diarrhea.
More information:
Grischa Chen et al., Cooperation between physiological defense and immune resistance produces asymptomatic carriage of a deadly bacterial pathogen, Scientific progress (2023). DOI: 10.1126/sciadv.adg8719. www.science.org/doi/10.1126/sciadv.adg8719
Quote: All Immunity, None of the Symptoms, Through Dietary Intervention (2023, June 23) Retrieved June 23, 2023 from https://medicalxpress.com/news/2023-06-immunity-symptoms-dietary-intervention.html
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