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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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 languageEnglish
Article number749074
Number of pages15
JournalFrontiers in Immunology
Publication statusPublished - 15 Nov 2021

Bibliographical note

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).

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.


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


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