GSE163533
Healthy peripheral neutrophils total RNA-Seq: Serum Amyloid P component is an essential element of resistance against Aspergillus fumigatus
Serum amyloid P component (SAP; APCS gene, also known as Pentraxin 2, PTX2), is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. The present study was designed to investigate the role of SAP/PTX2 in antifungal resistance. SAP-deficient Apcs-/- mice showed a dramatic increase in susceptibility to A. fumigatus infection. The defective anti-fungal resistance of gene targeted mice was rescued by in vitro opsonization of A.  fumigatus conidia and in vivo administration of murine SAP. Mouse and human SAP bound conidia, activated the complement cascade and increased phagocytosis by mouse and human neutrophils. Defective resistance of Apcs-/- SAP-deficient mice was associated with defective in vivo recruitment of neutrophils and phagocytosis in the lungs. The opsonic activity of SAP was dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protected 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 was associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus. The results reported here also suggest that SAP has therapeutic potential against an infectious agent which represents a formidable clinical challenge. Overall design: Whole transcriptome of sorted neutrophils derived from three healthy donors peripheral blood.