Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans

In this study, the human immune response mechanisms against Sporothrix brasiliensis and Sporothrix schenckii, two causative agents of human and animal sporotrichosis, were investigated. The interaction of S. brasiliensis and S. schenckii with human monocyte-derived macrophages (hMDMs) was shown to b...

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Autores principales:	Gabriela W. P. Neves, Sarah Sze Wah Wong, Vishukumar Aimanianda, Catherine Simenel, J. Iñaki Guijarro, Catriona Walls, Janet A. Willment, Neil A. R. Gow, Carol A. Munro, Gordon D. Brown, Leila M. Lopes-Bezerra
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Sporothrix schenckii Sporothrix brasiliensis complement receptor-3 (CR3) cell wall peptidorhamnomannan (PRM) human macrophages Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/bb4c4a4b11944c2dbe5e54c8ca580d0f
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spelling	oai:doaj.org-article:bb4c4a4b11944c2dbe5e54c8ca580d0f2021-11-15T06:50:41ZComplement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans1664-322410.3389/fimmu.2021.749074https://doaj.org/article/bb4c4a4b11944c2dbe5e54c8ca580d0f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.749074/fullhttps://doaj.org/toc/1664-3224In this study, the human immune response mechanisms against Sporothrix brasiliensis and Sporothrix schenckii, two causative agents of human and animal sporotrichosis, were investigated. The interaction of S. brasiliensis and S. schenckii with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of Sporothrix yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two Sporothrix yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the Sporothrix yeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1β secretion by hMDM in response to both S. brasiliensis and S. schenckii, suggesting that the host complement system plays an essential role in the inflammatory immune response against these Sporothrix species. Nevertheless, the structural differences in the PRMs of the two Sporothrix species, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system and via CR3 receptor mediating an inflammatory response to Sporothrix species.Gabriela W. P. NevesSarah Sze Wah WongVishukumar AimaniandaCatherine SimenelJ. Iñaki GuijarroCatriona WallsJanet A. WillmentJanet A. WillmentNeil A. R. GowNeil A. R. GowCarol A. MunroGordon D. BrownGordon D. BrownLeila M. Lopes-BezerraLeila M. Lopes-BezerraFrontiers Media S.A.articleSporothrix schenckiiSporothrix brasiliensiscomplement receptor-3 (CR3)cell wallpeptidorhamnomannan (PRM)human macrophagesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sporothrix schenckii Sporothrix brasiliensis complement receptor-3 (CR3) cell wall peptidorhamnomannan (PRM) human macrophages Immunologic diseases. Allergy RC581-607
spellingShingle	Sporothrix schenckii Sporothrix brasiliensis complement receptor-3 (CR3) cell wall peptidorhamnomannan (PRM) human macrophages Immunologic diseases. Allergy RC581-607 Gabriela W. P. Neves Sarah Sze Wah Wong Vishukumar Aimanianda Catherine Simenel J. Iñaki Guijarro Catriona Walls Janet A. Willment Janet A. Willment Neil A. R. Gow Neil A. R. Gow Carol A. Munro Gordon D. Brown Gordon D. Brown Leila M. Lopes-Bezerra Leila M. Lopes-Bezerra Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
description	In this study, the human immune response mechanisms against Sporothrix brasiliensis and Sporothrix schenckii, two causative agents of human and animal sporotrichosis, were investigated. The interaction of S. brasiliensis and S. schenckii with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of Sporothrix yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two Sporothrix yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the Sporothrix yeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1β secretion by hMDM in response to both S. brasiliensis and S. schenckii, suggesting that the host complement system plays an essential role in the inflammatory immune response against these Sporothrix species. Nevertheless, the structural differences in the PRMs of the two Sporothrix species, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system and via CR3 receptor mediating an inflammatory response to Sporothrix species.
format	article
author	Gabriela W. P. Neves Sarah Sze Wah Wong Vishukumar Aimanianda Catherine Simenel J. Iñaki Guijarro Catriona Walls Janet A. Willment Janet A. Willment Neil A. R. Gow Neil A. R. Gow Carol A. Munro Gordon D. Brown Gordon D. Brown Leila M. Lopes-Bezerra Leila M. Lopes-Bezerra
author_facet	Gabriela W. P. Neves Sarah Sze Wah Wong Vishukumar Aimanianda Catherine Simenel J. Iñaki Guijarro Catriona Walls Janet A. Willment Janet A. Willment Neil A. R. Gow Neil A. R. Gow Carol A. Munro Gordon D. Brown Gordon D. Brown Leila M. Lopes-Bezerra Leila M. Lopes-Bezerra
author_sort	Gabriela W. P. Neves
title	Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
title_short	Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
title_full	Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
title_fullStr	Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
title_full_unstemmed	Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans
title_sort	complement-mediated differential immune response of human macrophages to sporothrix species through interaction with their cell wall peptidorhamnomannans
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/bb4c4a4b11944c2dbe5e54c8ca580d0f
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Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans

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