Doni, AndreaParente, RaffaellaLaface, IlariaMagrini, ElenaCunha, CristinaColombo, Federico SimoneLacerda, JoãoCampos, AntónioMapelli, Sarah N.Petroni, FrancescaPorte, RémiSchorn, TiloInforzato, AntonioMercier, ToineLagrou, KatrienMaertens, JohanLambris, John D.Bottazzi, BarbaraGarlanda, CeciliaBotto, MarinaCarvalho, AgostinhoMantovani, Alberto2021-06-212021-06-212021Nat Commun. 2021 Jun 18;12(1):3739http://hdl.handle.net/10451/48675© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs-/- mice show enhanced susceptibility to A. fumigatus infection. Murine and human SAP bound conidia, activate the complement cascade and enhance phagocytosis by neutrophils. Apcs-/- mice are defective in vivo in terms of recruitment of neutrophils and phagocytosis in the lungs. Opsonic activity of SAP is dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protects hosts against A. fumigatus infection and death. In the context of a study of hematopoietic stem-cell transplantation, genetic variation in the human APCS gene is associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus.engjournal article10.1038/s41467-021-24021-y2041-1723