Front Immunol. 2018 Mar 21;9:567. doi: 10.3389/fimmu.2018.00567. eCollection 2018.
The Role of AIRE in the Immunity Against Candida Albicans in a Model of Human Macrophages
de Albuquerque JAT1, Banerjee PP2,3, Castoldi A1, Ma R2,3, Zurro NB1, Ynoue LH1, Arslanian C1, Barbosa-Carvalho MUW1, Correia-Deur JEM4, Weiler FG4, Dias-da-Silva MR4, Lazaretti-Castro M4, Pedroza LA5, Câmara NOS1, Mace E2,3, Orange JS2,3, Condino-Neto A1,6.
Author information:
1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
2. Center for Human Immunobiology, Texas Children's Hospital, Houston, TX, United States.
3. Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.
4. Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
5. Colegio de Ciencias de la Salud, Escuela de Medicina, Hospital de los Valles, Universidad San Francisco de Quito, Quito, Ecuador.
6. Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
Abstract
Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE). Patients with AIRE mutations are susceptible to Candida albicans infection and present with autoimmune disorders. We previously demonstrated that cytoplasmic AIRE regulates the Syk-dependent Dectin-1 pathway. In this study, we further evaluated direct contact with fungal elements, synapse formation, and the response of macrophage-like THP-1 cells to C. albicans hyphae to determine the role of AIRE upon Dectin receptors function and signaling. We examined the fungal synapse (FS) formation in wild-type and AIRE-knockdown THP-1 cells differentiated to macrophages, as well as monocyte-derived macrophages from APECED patients. We evaluated Dectin-2 receptor signaling, phagocytosis, and cytokine secretion upon hyphal stimulation. AIRE co-localized with Dectin-2 and Syk at the FS upon hyphal stimulation of macrophage-like THP-1 cells. AIRE-knockdown macrophage-like THP-1 cells exhibited less Dectin-1 and Dectin-2 receptors accumulation, decreased signaling pathway activity at the FS, lower C. albicans phagocytosis, and less lysosome formation. Furthermore, IL-1β, IL-6, or TNF-α secretion by AIRE-knockdown macrophage-like THP-1 cells and AIRE-deficient patient macrophages was decreased compared to control cells. Our results suggest that AIRE modulates the FS formation and hyphal recognition and help to orchestrate an effective immune response against C. albicans.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00567/full