It was quite the day for University of Florida College of Dentistry postdoctoral associate Marta Reguera Gómez, Ph.D., as her name was announced as the tied first-place winner in the postdoctoral research poster competition. At the Emerging Pathogens Institute Research Day 2025, Reguera Gómez accepted the award on behalf of the Martinez Lab for their dedicated work on fungal infection and immune response.
In this study, the team from the UF Department of Oral Biology focused on Cryptococcus neoformans, a fungus that can cause severe brain infections, especially in those with weakened immune systems. The team studied a specific immune molecule called interleukin-6 (IL-6), which helps keep the brain’s protective barrier strong and supports the body’s ability to fight off infections. Think of IL-6 as the coach and immune cells as the team — they can stimulate the movement of cells toward sites of inflammation, infection and trauma, but also stop an exacerbated response to maintain a balance in the organism.
To better understand IL-6’s role, the researchers compared three groups of mice: normal mice, mice that didn’t produce IL-6, and IL-6-deficient mice treated with lab-made IL-6. All the mice were infected with the fungus, and after one week, the team measured how much of the infection had spread to the lungs, blood and brain.
They found that mice without IL-6 died more quickly and had much higher levels of the fungus in their blood and brains. Although all groups had some lung inflammation, the brain showed significant differences among the groups. Mice with enough IL-6 had more active immune cells in the brain. In contrast, the IL-6-deficient mice had fewer protective responses and more signs of damaged brain cells. Without IL-6, the fungus spreads more easily, and the brain’s immune defenses are weakened. These findings suggest that boosting IL-6 could one day help treat or prevent brain infections in vulnerable patients.
Interestingly, the fungus seemed to react to IL-6 by growing a thicker capsule, which may be a way to defend itself. When asked about this double-edged effect, Reguera Gómez stated, “It makes sense: we need to remember that humans and their pathogens have coexisted for thousands of years. It is likely that over all these years, Cryptococcus has adapted to human immune pressures like IL-6.”
Using this study as a diving board, Reguera Gómez has already plunged into her next chapter. Moving to the Frias-Lopez Laboratory in the UF College of Dentistry, she now focuses on studying the genetic material (DNA) and the activity (RNA) of all the bacteria present in the oral cavity of patients with periodontitis.
“Since as a postdoc you never stop learning, I am currently working in metagenomics and transcriptomics of the oral microbiome,” said Reguera Gómez. “Let’s see where this path takes me! Receiving this award definitely boosted my energy to keep working towards excellence in my research. I am glad it shows my passion to communicate science.”
IL-6 deficiency accelerates cerebral cryptococcosis and alters glial cell responses
Collaborators
- Marta Reguera-Gomez – Department of Oral Biology, College of Dentistry, University of Florida
- Melissa E Munzen – Department of Oral Biology, College of Dentistry, University of Florida
- Mohammed F. Hamed – Department of Oral Biology, College of Dentistry, University of Florida
- Claudia L Charles-Nino – Department of Oral Biology, College of Dentistry, University of Florida
- Luis R. Martinez – Department of Oral Biology, Emerging Pathogens Institute, College of Dentistry, University of Florida
Introduction
Cryptococcus neoformans (Cn) is an opportunistic encapsulated fungal pathogen that causes life-threatening meningoencephalitis in immunosuppressed individuals. Interleukin-6 (IL-6) is crucial for blood-brain barrier integrity, and its deficiency has been shown to facilitate Cn brain invasion. This study investigates the impact of IL-6 on systemic Cn infection in vivo, focusing on central nervous system (CNS) colonization and glial responses, specifically microglia and astrocytes.
Methods
We utilized IL-6 knock-out (IL-6−/−) mice, wild-type C57BL/6 (WT) mice, and IL-6−/− mice supplemented with recombinant IL-6 (rIL-6; 40 pg/g/day). Mice were infected intravenously with C. neoformans strain H99. Fungal burdens in the lungs, blood, and brain tissues were quantified at 7 days postinfection using colony-forming unit (CFU) assays. Histological analyses assessed pulmonary inflammation and CNS involvement. 78 For the in vitro assays, C. neoformans was exposed to rIL-6 to evaluate capsule growth. Primary microglia-like cells were cultured with rIL-6 to assess phagocytosis and fungal killing, while IL-6 silencing was performed to determine its role in microglial function. Astrogliosis was evaluated using immunohistochemical staining for glial fibrillary acidic protein (GFAP).
Results
IL-6−/− mice exhibited faster mortality compared to WT and IL-6−/− mice supplemented with rIL-6. Early lung inflammation was observed across all groups, with no major histological differences in pulmonary cryptococcosis progression. However, IL-6−/− mice had significantly higher fungal burdens in blood and brain tissues at 7 days post-infection. In vitro exposure of C. neoformans to rIL-6 increased capsule size, suggesting a direct effect of IL-6 on the fungus. IL-6−/− brains showed an increased number of dystrophic microglia during Cn infection, which are associated with neurodegeneration and senescence. In contrast, the brains of IL-6-producing or IL-6-supplemented mice displayed high numbers of activated and phagocytic microglia, indicating a stronger anti-cryptococcal response or tissue repair. Microglia-like cells cultured with rIL-6 exhibited enhanced fungal phagocytosis and killing, whereas IL-6 silencing in microglia decreased fungal phagocytosis. Astrogliosis was pronounced in infected brains from WT mice and moderate in IL-6−/− mice supplemented with rIL-6, while minimal astrogliosis was observed in IL-6−/− tissue, highlighting the potential of astrocytes in containing and combating cryptococcal infection.
Conclusions
Our findings suggest a critical role for IL-6 in Cn CNS dissemination, neurocryptococcosis development, and host defense. IL-6 deficiency exacerbates CNS fungal invasion by impairing microglial and astrocytic responses. Enhancing IL-6 79 signaling may represent a therapeutic strategy to strengthen host defenses against cryptococcal infections in vulnerable populations.