A new study published in the Infectious Diseases & Immunity journal reveals how the lung's innate immune system is radically remodeled during Pneumocystis pneumonia (PCP) in the absence of adaptive immunity, identifying a specific macrophage subset as a promising target for future therapies.
PCP is a life-threatening fungal infection that primarily strikes individuals with weakened immune systems, such as those with HIV/AIDS or undergoing immunosuppressive therapy. However, how the body's first-line defense — the innate immune system — adapts when the adaptive immune system is absent has remained poorly understood.
Using single-cell RNA sequencing in a murine model of complete adaptive immunodeficiency, researchers discovered a significant expansion of a unique population: Ccr2 + monocyte-derived Nckap5 + macrophages. These cells exhibited strong anti-inflammatory features and activated pro-proliferative pathways, suggesting they play a complex role in disease progression.
Critically, the team demonstrated that pharmacologically inhibiting the MAPK pathway with Adezmapimod effectively reversed this expansion. This intervention significantly reduced the levels of Nckap5 and key anti-inflammatory cytokines, including Il10, Arg1, and Tgfβ — all associated with immune suppression.
These findings not only advance our understanding of PCP pathogenesis but also highlight Nckap5 + macrophages as a potential therapeutic target. They could pave the way for novel treatments aimed at modulating innate immune responses in immunocompromised patients, where traditional therapies often fall short.
The study provides a foundational resource for developing targeted interventions against this severe fungal infection.
Infectious Diseases & Immunity
Experimental study
Animals
Pulmonary innate immune remodeling in Pneumocystis pneumonia with adaptive immunodeficiency
9-Jun-2026