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The Cryptococcus neoformans species complex (CNSC) is a common opportunistic human fungal pathogen and the most frequent cause of fungal meningitis. There are three major serotypes in CNSC: A, D, and their hybrids AD, and they have different geographic distributions and medical significance. Melanin pigment and a polysaccharide capsule are the two major virulence factors in CNSC. However, the relationships between serotype and virulence factor production and how environmental factors might impact their relationships are not known. This study investigated the expressions of melanin and capsular polysaccharide in a genetically diverse group of CNSC strains and how their phenotypic expressions were influenced by oxidative and nitrosative stress levels. We found significant differences in melanin and capsular polysaccharide productions among serotypes and across stress conditions. Under oxidative stress, the laboratory hybrids exhibited the highest phenotypic plasticity for melanin production while serotype A showed the highest for capsular polysaccharide production. In contrast, serotype D exhibited the highest phenotypic plasticity for capsular polysaccharide production and clinical serotype AD the highest phenotypic plasticity for melanin production under nitrosative stress. These results demonstrated that different serotypes have different environmental condition-specific mechanisms to modulate the expression of virulence factors.

Personality has been correlated with differences in cytokine expression, an indicator of peripheral inflammation; however, the associations between personality and central markers of inflammation have never been investigated in vivo in humans. Microglia are the resident macrophages of the central nervous system, and the first responders to tissue damage and brain insult. Microglial activation is associated with elevated expression of translocator protein 18kDa (TSPO), which can be imaged with positron emission tomography (PET) to quantify immune activation in the human brain. This study aimed to investigate the association between personality and TSPO expression across the psychosis spectrum. A total of 61 high-resolution [18F]FEPPA PET scans were conducted in 28 individuals at clinical high risk (CHR) for psychosis, 19 First-Episode Psychosis (FEP), and 14 healthy volunteers (HVs), and analyzed using a two-tissue compartment model and plasma input function to obtain a total volume of distribution (VT) as an index of brain TSPO expression (controlling for the rs6971 TSPO polymorphism). Personality was assessed using the Revised NEO Personality Inventory (NEO-PI-R). We found TSPO expression to be specifically associated with neuroticism. A positive association between TSPO expression and neuroticism was found in HVs, in contrast to a nonsignificant, negative association in CHR and significant negative association in FEP. The TSPO-associated neuroticism trait indicates an unexplored connection between neuroimmune activation and personality that varies across the psychosis spectrum.