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

Gabriela W.P.  Neves; Sarah Sze Wah  Wong; Vishukumar Aimanianda; Catherine  Simenel; J. Iñaki  Guijarro; Catriona Walls; Janet Anne Willment; Neil A.R.  Gow; Carol Munro; Gordon Brown; Leila Maria Lopes Bezerra

doi:10.3389/fimmu.2021.749074

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

Gabriela W.P. Neves, Sarah Sze Wah Wong, Vishukumar Aimanianda, Catherine Simenel, J. Iñaki Guijarro, Catriona Walls, Janet Anne Willment, Neil A.R. Gow, Carol Munro, Gordon Brown, Leila Maria Lopes Bezerra^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

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 (hMDM) 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 pathogen25 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). Further, the blockade of CR3 specifically impacted the 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.

Original language	English
Article number	749074
Number of pages	15
Journal	Frontiers in Immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.749074
Publication status	Published - 15 Nov 2021

Bibliographical note

Funding
This work was supported by Fundação de Apoio à Pesquisa do Distrito Federal (FAP-DF)/CNPq, PRONEX grant ID: (FAP-DF, 0193.001.200/2016). VA is supported by the Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA) grant No. 5403-1 and ANR-DFG AfuINF grant. IG, VA, and CS were supported by the ANR-FUNHYDRO (ANR-16S-CE110020-01) grant. NG, GB and JW are supported by the Welcome Trust (102705, 097377, 101873, 215599 and 200208) and the Medical Research Council Centre for Medical Mycology (MR/N006364/2).

Acknowledgments
The authors acknowledge Dr. Lars Erwig, Dr. Jude Bain, and Dr. Kevin MacKenzie of University of Aberdeen for the scientific and technical support in the video microscopy experiments. LMLB was a research fellow of Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge Fundação Carlos Chagas Filho de Amparo a Pesquisa do estado do Rio de Janeiro (Faperj) and Pasteur-Roux-Cantarini postdoctoral fellowship for the research fellowships given to GWPN and SSWW, respectively.

Keywords

Sporothrix schenckii
Sporothrix brasiliensis
Complement receptor-3 (CR3)
Cell wall
Peptidorhamnomannan (PRM)
Human macrophages
Innate immune response

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Neves, G. W. P., Wong, S. S. W., Aimanianda, V., Simenel, C., Guijarro, J. I., Walls, C., Willment, J. A., Gow, N. A. R., Munro, C., Brown, G., & Lopes Bezerra, L. M. (2021). Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans. Frontiers in Immunology, 12, Article 749074. https://doi.org/10.3389/fimmu.2021.749074

Neves, GWP, Wong, SSW, Aimanianda, V, Simenel, C, Guijarro, JI, Walls, C, Willment, JA, Gow, NAR, Munro, C, Brown, G & Lopes Bezerra, LM 2021, 'Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans', Frontiers in Immunology, vol. 12, 749074. https://doi.org/10.3389/fimmu.2021.749074

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

abstract = "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 (hMDM) was shown tobe 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 pathogen25 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). Further, the blockade of CR3 specifically impacted the 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.",

keywords = "Sporothrix schenckii, Sporothrix brasiliensis, Complement receptor-3 (CR3), Cell wall, Peptidorhamnomannan (PRM), Human macrophages, Innate immune response",

author = "Neves, {Gabriela W.P.} and Wong, {Sarah Sze Wah} and Vishukumar Aimanianda and Catherine Simenel and Guijarro, {J. I{\~n}aki} and Catriona Walls and Willment, {Janet Anne} and Gow, {Neil A.R.} and Carol Munro and Gordon Brown and {Lopes Bezerra}, {Leila Maria}",

note = "Funding This work was supported by Funda{\c c}{\~a}o de Apoio {\`a} Pesquisa do Distrito Federal (FAP-DF)/CNPq, PRONEX grant ID: (FAP-DF, 0193.001.200/2016). VA is supported by the Centre Franco-Indien pour la Promotion de la Recherche Avanc{\'e}e (CEFIPRA) grant No. 5403-1 and ANR-DFG AfuINF grant. IG, VA, and CS were supported by the ANR-FUNHYDRO (ANR-16S-CE110020-01) grant. NG, GB and JW are supported by the Welcome Trust (102705, 097377, 101873, 215599 and 200208) and the Medical Research Council Centre for Medical Mycology (MR/N006364/2). Acknowledgments The authors acknowledge Dr. Lars Erwig, Dr. Jude Bain, and Dr. Kevin MacKenzie of University of Aberdeen for the scientific and technical support in the video microscopy experiments. LMLB was a research fellow of Funda{\c c}{\~a}o de Amparo a Pesquisa do Estado de S{\~a}o Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq). We acknowledge Funda{\c c}{\~a}o Carlos Chagas Filho de Amparo a Pesquisa do estado do Rio de Janeiro (Faperj) and Pasteur-Roux-Cantarini postdoctoral fellowship for the research fellowships given to GWPN and SSWW, respectively. ",

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doi = "10.3389/fimmu.2021.749074",

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AU - Neves, Gabriela W.P.

AU - Wong, Sarah Sze Wah

AU - Aimanianda, Vishukumar

AU - Simenel, Catherine

AU - Guijarro, J. Iñaki

AU - Walls, Catriona

AU - Willment, Janet Anne

AU - Gow, Neil A.R.

AU - Munro, Carol

AU - Brown, Gordon

AU - Lopes Bezerra, Leila Maria

N1 - Funding This work was supported by Fundação de Apoio à Pesquisa do Distrito Federal (FAP-DF)/CNPq, PRONEX grant ID: (FAP-DF, 0193.001.200/2016). VA is supported by the Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA) grant No. 5403-1 and ANR-DFG AfuINF grant. IG, VA, and CS were supported by the ANR-FUNHYDRO (ANR-16S-CE110020-01) grant. NG, GB and JW are supported by the Welcome Trust (102705, 097377, 101873, 215599 and 200208) and the Medical Research Council Centre for Medical Mycology (MR/N006364/2). Acknowledgments The authors acknowledge Dr. Lars Erwig, Dr. Jude Bain, and Dr. Kevin MacKenzie of University of Aberdeen for the scientific and technical support in the video microscopy experiments. LMLB was a research fellow of Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge Fundação Carlos Chagas Filho de Amparo a Pesquisa do estado do Rio de Janeiro (Faperj) and Pasteur-Roux-Cantarini postdoctoral fellowship for the research fellowships given to GWPN and SSWW, respectively.

PY - 2021/11/15

Y1 - 2021/11/15

N2 - 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 (hMDM) was shown tobe 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 pathogen25 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). Further, the blockade of CR3 specifically impacted the 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.

AB - 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 (hMDM) was shown tobe 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 pathogen25 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). Further, the blockade of CR3 specifically impacted the 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.

KW - Sporothrix schenckii

KW - Sporothrix brasiliensis

KW - Complement receptor-3 (CR3)

KW - Cell wall

KW - Peptidorhamnomannan (PRM)

KW - Human macrophages

KW - Innate immune response

U2 - 10.3389/fimmu.2021.749074

DO - 10.3389/fimmu.2021.749074

M3 - Article

SN - 1664-3224

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 749074

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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