The C-type lectin receptor Dcir (Clec4a2) restrains Aspergillus fumigatus elimination by limiting the degranulatory activity of neutrophils

Fabio Seiti Yamada Yoshikawa^1*Rikio Yabe²SHOTA TORIGOE³Sho Yamasaki⁴Shinobu Saijo^1*

• ¹Chiba University, Chiba, Japan
• ²Tokyo Metropolitan Institute of Medical Science, tokyo, Japan
• ³National Institute of Infectious Disease, Tokyo, Japan
• ⁴Osaka Daigaku, Suita, Japan

C-type lectin receptors (CLRs) are innate sensors crucial for antifungal and antimycobacterial responses, contributing to host defenses against pathogens, including the ubiquitous mold Aspergillus fumigatus. Dendritic cell immunoreceptor (Dcir) modulates immune responses by limiting the development of inflammation and autoimmunity; however, its involvement in fungal infections has not been previously established. In this study, mice lacking Dcir exhibited improved clearance of A. fumigatus from the lungs, while tissue inflammation—assessed by phagocyte recruitment and inflammatory cytokine levels within the lungs—did not change significantly compared to Dcir-competent mice. Neutrophils from Dcir-deficient mice exhibited enhanced killing of A. fumigatus hyphae, attributed to higher degranulatory activity. The results indicate a potential association between Dcir and downregulation of signaling pathways associated with neutrophil exocytosis, triggered by intracellular Ca2+ mobilization. Thus, Dcir is a potential novel fungal sensor that, unlike other CLR family members, primarily fine-tunes host effector responses.