Differential interactions of serum and bronchoalveolar lavage complement proteins with conidia of airborne fungal pathogen Aspergillus fumigatus.

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Differential interactions of serum and bronchoalveolar lavage complement proteins with conidia of airborne fungal pathogen Aspergillus fumigatus.

Infect Immun. 2020 Jun 22;:

Authors: Wong SSW, Daniel I, Gangneux JP, Jayapal JM, Guegan H, Dellière S, Lalitha P, Shende R, Madan T, Bayry J, Guijarro JI, Kuppamuthu D, Aimanianda V

Abstract
Even though both cellular and humoral immunities contribute to host defense, the role played by humoral immunity against the airborne opportunistic fungal pathogen Aspergillus fumigatus has been underexplored. In this study, we aimed at deciphering the role of complement-system, the major humoral immune component, against A. fumigatus Mass-spectrometric analysis of the proteins extracted from A. fumigatus conidial (asexual spores and infective propagules) surfaces opsonized with human serum indicated that C3 is the major complement protein involved. Flow cytometry and immunolabelling assays further confirmed C3b (activated C3) deposition on the conidial surfaces. Assays using cell wall components of conidia indicated that the hydrophobin RodAp, β-(1,3)-glucan (BG) and galactomannan (GM) could efficiently activate C3. Using complement component-depleted sera, we show that while RodAp activated C3 by the alternative pathway, BG and GM partially follow the classical and lectin pathways, respectively. Opsonization facilitated conidial aggregation and phagocytosis, and complement receptors (CR3 and CR4) blockage on phagocytes significantly inhibited phagocytosis, indicating that the complement-system exerts a protective role against conidia by opsonizing them and facilitating their phagocytosis mainly through complement receptors. Conidial opsonization with human bronchoalveolar lavage fluid (BALF) confirmed C3 to be the major complement protein interacting. Nevertheless, complement C2 and mannose binding lectin (MBL), the classical and lectin pathway components respectively, were not identified, indicating that BALF activates the alternative pathway on the conidial surface. Moreover, the cytokine profiles were different upon stimulation of phagocytes with serum or BALF opsonized conidia, highlighting the importance of studying the conidial interaction in their biological niche.

PMID: 32571987 [PubMed – as supplied by publisher]

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