Postdoctoral fellow Harbor-UCLA Medical Center Torrance, California, United States
Disclosure(s):
Jian Miao, PhD: No financial relationships to disclose
Introduction/Rationale: Neonates possess a developing immune system, which is different from adults as a result of initially living in a semi-allogeneic sterile environment to then being exposed to a microbial-rich surrounding, rendering newborns highly susceptible to infections. Following microbial exposure, the mucosal immune system of neonates goes through successive, non-redundant phases that support the developmental needs of the infant to establish immune homeostasis. However, it remains unknown how neonates prevent fungal outgrowth during colonization, representing a critical gap in knowledge.
Methods: To address this, we developed a novel mouse model of neonatal commensal Candida albicans colonization that results in persistent fungal presence. Single cell RNA sequencing was utilized to obtain a comprehensive view of gene expression dynamics.
Results: Early during colonization, proinflammatory cytokines were downregulated with increased porpotion of CD25+ Foxp3+ Treg and CD25+ Foxp3- T cells, likely to mitigate excessive immune activation and promote tolerance. Unexpectedly, CCL11 levels were elevated during early fungal persistence. Neutralization of CCL11 reduced oral fungal burden, suggesting a role in mediating tolerance. Later during colonization, IL-22-mediated immunity and associated tissue remodeling plays a critical role in controlling fungal burden and preventing fungal invasion. Furthermore, single-cell RNA sequencing revealed dynamic shifts in immune cell subpopulations over time.
Conclusion: In summary, neonatal fungal colonization elicits dynamic immune responses that contribute to maintaining homeostasis at the oral mucosal barrier.
