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The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis

Serum amyloid P component (SAP) may play an important role in human fungal diseases. SAP binds to functional amyloid on the fungal surface and masks fungi from host immune processes, skewing the macrophage population from the pro-inflammatory M1 to the quiescent M2 type. We assessed the role of SAP...

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Autores principales: Klotz, Stephen A., Lipke, Peter N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697064/
https://www.ncbi.nlm.nih.gov/pubmed/36365055
http://dx.doi.org/10.3390/pathogens11111304
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author Klotz, Stephen A.
Lipke, Peter N.
author_facet Klotz, Stephen A.
Lipke, Peter N.
author_sort Klotz, Stephen A.
collection PubMed
description Serum amyloid P component (SAP) may play an important role in human fungal diseases. SAP binds to functional amyloid on the fungal surface and masks fungi from host immune processes, skewing the macrophage population from the pro-inflammatory M1 to the quiescent M2 type. We assessed the role of SAP in a murine model of disseminated candidiasis. Mice were injected with human SAP subcutaneously (SQ) followed by intravenous injection of Candida albicans. Male, BALBcJ mice were administered 2 mg human SAP or the homologous human pro-inflammatory pentraxin CRP, SQ on day −1 followed by 1 mg on days 0 thru 4; yeast cells were administered intravenously on day 0. Mice not receiving a pentraxin were morbid on day 1, surviving 4–7 days. Mice administered SAP survived longer than mice receiving yeast cells alone (p < 0.022), although all mice died. Mice given CRP died faster than mice receiving yeast cells alone (p < 0.017). Miridesap is a molecule that avidly binds SAP, following which the complex is broken down by the liver. Miridesap administered in the drinking water removed SAP from the serum and yeast cells and significantly prolonged the life of mice (p < 0.020). Some were “cured” of candidiasis. SAP administered early in the septic process provided short-lived benefit to mice, probably by blunting cytokine secretion associated with disseminated candidiasis. The most important finding was that removal of SAP with miridesap led to prolonged survival by removing SAP and preventing its dampening effects on the host immune response.
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spelling pubmed-96970642022-11-26 The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis Klotz, Stephen A. Lipke, Peter N. Pathogens Article Serum amyloid P component (SAP) may play an important role in human fungal diseases. SAP binds to functional amyloid on the fungal surface and masks fungi from host immune processes, skewing the macrophage population from the pro-inflammatory M1 to the quiescent M2 type. We assessed the role of SAP in a murine model of disseminated candidiasis. Mice were injected with human SAP subcutaneously (SQ) followed by intravenous injection of Candida albicans. Male, BALBcJ mice were administered 2 mg human SAP or the homologous human pro-inflammatory pentraxin CRP, SQ on day −1 followed by 1 mg on days 0 thru 4; yeast cells were administered intravenously on day 0. Mice not receiving a pentraxin were morbid on day 1, surviving 4–7 days. Mice administered SAP survived longer than mice receiving yeast cells alone (p < 0.022), although all mice died. Mice given CRP died faster than mice receiving yeast cells alone (p < 0.017). Miridesap is a molecule that avidly binds SAP, following which the complex is broken down by the liver. Miridesap administered in the drinking water removed SAP from the serum and yeast cells and significantly prolonged the life of mice (p < 0.020). Some were “cured” of candidiasis. SAP administered early in the septic process provided short-lived benefit to mice, probably by blunting cytokine secretion associated with disseminated candidiasis. The most important finding was that removal of SAP with miridesap led to prolonged survival by removing SAP and preventing its dampening effects on the host immune response. MDPI 2022-11-06 /pmc/articles/PMC9697064/ /pubmed/36365055 http://dx.doi.org/10.3390/pathogens11111304 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Klotz, Stephen A.
Lipke, Peter N.
The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title_full The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title_fullStr The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title_full_unstemmed The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title_short The Paradoxical Effects of Serum Amyloid-P Component on Disseminated Candidiasis
title_sort paradoxical effects of serum amyloid-p component on disseminated candidiasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697064/
https://www.ncbi.nlm.nih.gov/pubmed/36365055
http://dx.doi.org/10.3390/pathogens11111304
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