Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

Andrea Doni, Raffaella Parente, Ilaria Laface, Elena Magrini, Cristina Cunha, Federico Simone Colombo, João F. Lacerda, António Campos, Sarah N. Mapelli, Francesca Petroni, Rémi Porte, Tilo Schorn, Antonio Inforzato, Toine Mercier, Katrien Lagrou, Johan Maertens, John D. Lambris, Barbara Bottazzi, Cecilia Garlanda, Marina Botto, Agostinho Carvalho and Alberto Mantovani ()
Additional contact information
Andrea Doni: IRCCS Humanitas Research Hospital, via Manzoni 56
Raffaella Parente: IRCCS Humanitas Research Hospital, via Manzoni 56
Ilaria Laface: IRCCS Humanitas Research Hospital, via Manzoni 56
Elena Magrini: IRCCS Humanitas Research Hospital, via Manzoni 56
Cristina Cunha: University of Minho
Federico Simone Colombo: IRCCS Humanitas Research Hospital, via Manzoni 56
João F. Lacerda: Faculdade de Medicina de Lisboa
António Campos: Instituto Português de Oncologia do Porto
Sarah N. Mapelli: IRCCS Humanitas Research Hospital, via Manzoni 56
Francesca Petroni: IRCCS Humanitas Research Hospital, via Manzoni 56
Rémi Porte: IRCCS Humanitas Research Hospital, via Manzoni 56
Tilo Schorn: IRCCS Humanitas Research Hospital, via Manzoni 56
Antonio Inforzato: IRCCS Humanitas Research Hospital, via Manzoni 56
Toine Mercier: University Hospitals Leuven
Katrien Lagrou: Immunology and Transplantation, KU Leuven
Johan Maertens: University Hospitals Leuven
John D. Lambris: University of Pennsylvania
Barbara Bottazzi: IRCCS Humanitas Research Hospital, via Manzoni 56
Cecilia Garlanda: IRCCS Humanitas Research Hospital, via Manzoni 56
Marina Botto: Imperial College London
Agostinho Carvalho: University of Minho
Alberto Mantovani: IRCCS Humanitas Research Hospital, via Manzoni 56

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24021-y

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