Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9 -/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9 -/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans.

Mental health disparities in the aftermath of national disasters and the protective role of socioeconomic status are both well documented. We assessed the prevalence of depression and anxiety symptoms among underresourced public university students during the COVID‐19 pandemic in New York City. Between April 8, 2020, and May 2, 2020, adult students ( N = 1,821) across the CUNY system completed an online survey examining COVID‐19–related stressors and mental health and sociodemographic factors. Using multivariable logistical regression to assess the association between COVID‐19–related stressors and depression and anxiety symptoms, we found a high prevalence and severity of depression and anxiety symptoms. We also observed that more exposure to COVID‐19–related stressors was associated with increased depressive (27.0%, 41.4%, and 63.1% for low‐, medium‐, and high‐level stressors, respectively) and anxiety symptoms (19.3%, 34.6%, 52.2%). In addition, the degree of exposure to COVID‐19–related stressors served as an important predictor of depression and anxiety symptoms. Compared to high levels of stressors, the odds of depression were 0.2, 95% CI [0.2, 0.3] for low‐ and 0.4, 95% CI [0.3, 0.5] for medium‐level stressors; for anxiety, the odds were 0.2, 95% CI [0.2, 0.3] for low and 0.05, 95% CI [0.4, 0.6] for medium stressors. Finally, household savings of less than $5,000 increased the risk of anxiety but not depression symptoms, OR = 1.3, 95% CI [1.0,1.6]. Together, these findings tell a devastating story of psychological distress among students from lower socioeconomic groups living in the COVID‐19 epicenter of the U.S. pandemic.

Allergic disease prevalence has significantly increased in recent decades. Primary prevention efforts are being guided by the study of the exposome, or collective environmental exposures beginning during the prenatal period, to identify modifiable factors that impact allergic disease risk. In this review, we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their impact on atopy development, focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life may also impact disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all individuals. Understanding the impact of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.

Background Signaling defects in the Toll-like receptor (TLR) pathway, such as interleukin-1 receptor–associated kinase 4 deficiency, highlight the prominence of TLR signaling in the defense against bacterial disease. Because myeloid differentiation primary response gene 88 (MyD88) can transduce signals from almost all TLRs, we studied its role in otitis media (OM), the most common upper respiratory tract bacterial infectious disease in young children. Methods The middle ears (MEs) of wild-type (WT) and MyD88−/− mice were inoculated with nontypeable Haemophilus influenzae (NTHi). ME infection and inflammation were monitored for 21 days after surgery. Bone marrow–derived macrophages from WT and MyD88−/− mice were infected with NTHi in vitro to assess their interaction with bacteria. Results In WT mice, MyD88 expression was detected in the ME stroma at baseline. MyD88−/− mice displayed prolonged ME mucosal thickening and delayed recruitment of neutrophils and macrophages. Although WT mice cleared NTHi within 5 days, viable NTHi were isolated for up to 21 days in MyD88−/− mice. The interaction between macrophages and NTHi was significantly altered in MyD88−/− mice. Conclusions In this mouse model, MyD88-mediated signaling was important for clearance of infection and resolution of inflammation in acute OM due to NTHi. The role played by innate signaling in children susceptible to chronic or recurrent OM deserves further study.