Abstract
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.
Highlights
Serum amyloid P component (SAP, 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
SAP is essential for resistance to A. fumigatus infection
Apcs−/− mice showed lethal infection with a median survival time (MST) of 3 days compared to MST > 10 days of wt, both when 1 × 108 (Fig. 1a) or 5 × 107 (Fig. 1b) conidia were used
Summary
Serum amyloid P component (SAP, 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. Humoral pattern recognition molecules (PRMs) are essential components of the innate immune response sharing functional outputs with antibodies[3], including opsonisation, regulation of complement activation, agglutination, and neutralization[1]. SAP has complex biological functions that include regulation of matrix formation and resistance to infectious agents[8,10]. These general functions are shared by other pentraxins[11,12,13,14].
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