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Nature communications
06 18, 2021;12 (1): 3739.

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, Alberto Mantovani
Author Information
  1. Andrea Doni: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  2. Raffaella Parente: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. ORCID
  3. Ilaria Laface: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  4. Elena Magrini: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  5. Cristina Cunha: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. ORCID
  6. Federico Simone Colombo: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. ORCID
  7. João F Lacerda: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
  8. António Campos: Serviço de Transplantação de Medula Óssea (STMO), Instituto Português de Oncologia do Porto, Porto, Portugal.
  9. Sarah N Mapelli: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  10. Francesca Petroni: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  11. Rémi Porte: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  12. Tilo Schorn: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy.
  13. Antonio Inforzato: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. ORCID
  14. Toine Mercier: Department of Hematology, University Hospitals Leuven, Leuven, Belgium. ORCID
  15. Katrien Lagrou: Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. ORCID
  16. Johan Maertens: Department of Hematology, University Hospitals Leuven, Leuven, Belgium. ORCID
  17. John D Lambris: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  18. Barbara Bottazzi: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. ORCID
  19. Cecilia Garlanda: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. ORCID
  20. Marina Botto: Department of Immunology and Inflammation, Imperial College London, London, UK. ORCID
  21. Agostinho Carvalho: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. ORCID
  22. Alberto Mantovani: IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan, Italy. alberto.mantovani@humanitasresearch.it. ORCID
PMID: 34145258 DOI: 10.1038/s41467-021-24021-y

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.

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MeSH Term

Animals
Aspergillus fumigatus
Cells, Cultured
Genetic Variation
Humans
Immunity, Innate
Immunocompromised Host
Invasive Pulmonary Aspergillosis
Lung
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Phagocytosis
Serum Amyloid P-Component

Chemicals

Serum Amyloid P-Component
Journal Article Research Support, Non-U.S. Gov't

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