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

Sarah Sze Wah Wong (1) , Irene Daniel (2) , J-P Gangneux (3) , Jeya Maheshwari Jayapal (2) , Hélène Guegan (3) , Sarah Dellière (1, 4) , Prajna Lalitha (5) , Rajashri Shende (6) , Taruna Madan (7) , Jagadeesh Bayry (8) , J. Inaki Guijarro (9) , Dharmalingam Kuppamuthu (2) , Vishukumar Aimanianda (1)

1 Mycologie moléculaire - Molecular Mycology
2 AMRF - Aravind Medical Research Foundation
3 Irset - Institut de recherche en santé, environnement et travail
4 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
5 Aravind Eye Hospital [Madurai, India]
6 Savitribai Phule Pune University [India]
7 ICMR - Indian Council of Medical Research [New Dehli]
8 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
9 Plateforme technologique de RMN biologique - Biological NMR Technological Platform

Even though both cellular and humoral immunities contribute to host defense, the role played by humoral immunity against the airborne opportunistic fungal pathogen has been underexplored. In this study, we aimed at deciphering the role of the complement system, the major humoral immune component, against Mass spectrometry analysis of the proteins extracted from conidial (asexual spores and infective propagules) surfaces opsonized with human serum indicated that C3 is the major complement protein involved. Flow cytometry and immunolabeling 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 showed that while RodAp activates C3 by the alternative pathway, BG and GM partially follow the classical and lectin pathways, respectively. Opsonization facilitated conidial aggregation and phagocytosis, and complement receptor (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 with conidia. 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- and BALF-opsonized conidia, highlighting the importance of studying interaction of conidia with complement proteins in their biological niche.

Mots clés: Aspergillus fumigatus; Aspergillus fumigatus conidia; cell wall; complement receptors; complement system; cytokines; host-pathogen interactions; humoral immunity; macrophages; polysaccharides; proteomics

Domaines: Immunité adaptative; Maladies infectieuses

Sarah Sze Wah Wong, Irene Daniel, J-P Gangneux, Jeya Maheshwari Jayapal, Hélène Guegan, et al.. Differential interactions of serum and bronchoalveolar lavage complement proteins with conidia of airborne fungal pathogen Aspergillus fumigatus. Infection and Immunity, 2020, 88 (9), ⟨10.1128/IAI.00212-20⟩. ⟨hal-02888806⟩