The Noverr laboratory focuses on investigating mechanisms of immunomodulation and inflammation by the fungal pathogen Candida albicans and non-albicans Candida species (NAC) during host-pathogen interactions. The majority of humans are chronically colonized at various mucosal surfaces with Candida and NAC. These fungal pathogens can cause a variety of infections, ranging from mucosal to systemic/invasive candidiasis. The overall goal of the laboratory is to understand mechanisms of Candida pathogenesis and immunomodulation in mucosal and systemic infections. This includes investigating in vivo models of biofilm formation at mucosal surfaces, both during experimental vaginitis and denture stomatitis. These models allow investigation of host, bacterial, and fungal factors that affect Candida biofilms in a clinically relevant setting. C. albicans and NAC are a frequent cause of polymicrobial infections with bacterial pathogens. We have developed a polymicrobial intra-abdominal infection (IAI) model with C. albicans and S. aureus, two pathogens that inhabit the same niches in the host, and that cause synergistic effects on mortality and promote sepsis. Investigation of the host response revealed a key role for PGE2 in promoting inflammation and mortality, which brings the focus back to a key strength of the laboratory, eicosanoid research. We have also discovered that low virulence NAC species induce protective immunity against highly lethal polymicrobial IAI. Rather than adaptive immunity, this protection is dependent on long-lived Gr-1+ leukocytes, suggestive of a novel form of trained innate immunity mediated by myeloid-derived suppressor cells (MDSCs). Current projects in the lab are focused on investigating both mechanisms of infectious synergy between C. albicans and S. aureus, and mechanisms of trained innate immunity against polymicrobial sepsis induced by low virulence NAC.
- Fungal Pathogenesis
- Polymicrobial intra-abdominal infection and sepsis
- Trained Innate Immunity Vaccine Strategies
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