October 28, 2025 | By Asher Jones
In the early 1900s, a cluster of typhoid cases and several deaths among wealthy families in Manhattan sparked alarm. Investigators, after ruling out potential causes such as contaminated water, noticed that the families had something in common: They’d all hired a cook named Mary Mallon. Now better known as Typhoid Mary, she likely infected more than 100 people with typhoid-causing Salmonella bacteria while remaining asymptomatic herself.
Mallon is t
he classic example of a superspreader. Understanding how superspreaders tolerate high pathogen loads while remaining symptom-free intrigues Blanda Di Luccia, a new Research Assistant Professor in the Department of Immunology.
“Salmonella is a systemic disease that spreads beyond the gut to the bloodstream and other organs, but my interest is in the mucosal tissue,” said Di Luccia. “How do intestinal mucosa and immune cells respond to Salmonella in superspreaders? There is a lot to uncover.”
In a new study, published in the Journal of Experimental Medicine, researchers led by Di Luccia and Denise Monack at Stanford University show that a population of regulatory T cells (Tregs) enable superspreader mice to remain symptom-free, despite having high loads of Salmonella in the gut.
They found that superspreader mice had high levels of unique Tregs that expressed a transcription factor called T-bet. These regulatory cells suppress cytotoxic CD4+ T cells that express a molecule called granzyme B, which causes intestinal damage.
“Superspreader mice have inflamed guts full of T cells producing inflammatory cytokines but display no signs of gastroenteritis,” Di Luccia explained. “The inflammation is counterbalanced by regulatory T cells.”
When the researchers depleted Tregs, cytotoxic CD4+ T cells increased and the mice quickly developed symptoms of Salmonella infection: increased gut inflammation, impairment of the intestinal barrier, rapid weight loss, and decreased survival.
According to Di Luccia, who will continue this research at Pitt, understanding how Tregs and other immune cells maintain tolerance in the face of chronic inflammation has wide-ranging implications for inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.
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Image 1: Blanda Di Luccia, Research Assistant Professor in the Department of Immunology at the Pitt School of Medicine
Image 2: Colonic tissue of asymptomatic superspreader mice with high levels of Salmonella (left). When regulatory T cells are depleted (right) mice show gastroenteritis symptoms and there is an increase in tissue-damaging cytotoxic CD4+ T cells (depicted by arrows), which localize to the epithelium. [Credit: Di Luccia et al., 2025, JEM]