Sustained Club Cell Injury in Mice Induces Histopathologic Features of Deployment-Related Constrictive Bronchiolitis.

Histopathologic evidence of deployment-related constrictive bronchiolitis (DRCB) has been identified in soldiers deployed to Southwest Asia. While inhalational injury to the airway epithelium is suspected, relatively little is known about the pathogenesis underlying this disabling disorder. Club cells are local progenitors critical for repairing the airway epithelium after exposure to various airborne toxins, and a prior study using an inducible transgenic murine model reported that 10 days of sustained targeted club cell injury causes constrictive bronchiolitis.

Autocrine IL-10 Signaling Promotes Dendritic Cell Type-2 Activation and Persistence of Murine Cryptococcal Lung Infection.

The substantial morbidity and mortality caused by invasive fungal pathogens, including , necessitates increased understanding of protective immune responses against these infections. Our previous work using murine models of cryptococcal lung infection demonstrated that dendritic cells (DCs) orchestrate critical transitions from innate to adaptive immunity and that IL-10 signaling blockade improves fungal clearance. To further understand interrelationships among IL-10 production, fungal clearance, and the effect of IL-10 on lung DCs, we performed a comparative temporal analysis of cryptococcal lung infection in wild type C57BL/6J mice (designated IL-10) and IL-10 mice inoculated intratracheally with (strain 52D).

Anti-PD-1 Antibody Treatment Promotes Clearance of Persistent Cryptococcal Lung Infection in Mice.

Activation of immunomodulatory pathways in response to invasive fungi can impair clearance and promote persistent infections. The programmed cell death protein-1 (PD-1) signaling pathway inhibits immune effector responses against tumors, and immune checkpoint inhibitors that block this pathway are being increasingly used as cancer therapy. The objective of this study was to investigate whether this pathway contributes to persistent fungal infection and to determine whether anti-PD-1 Ab treatment improves fungal clearance.