The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response

Author(s):Show less -

Salgado, Ranieri Coelho ^[1] ; Fonseca, Dennyson Leandro M. ^[2] ; Marques, Alexandre H. C. ^[2] ; da Silva Napoleao, Sarah Maria ^[1] ; Franca, Tabata Takahashi ^[1] ; Akashi, Karen Tiemi ^[2] ; de Souza Prado, Caroline Aliane ^[2] ; Baiocchi, Gabriela Crispim ^[1] ; Placa, Desiree Rodrigues ^[2] ; Jansen-Marques, Gabriel ^[3] ; Filgueiras, Igor Salerno ^[1] ; De Vito, Roberta ^{[4, 5]} ; Freire, Paula Paccielli ^[1] ; de Miranda, Gustavo Cabral ^[1] ; Saraiva Camara, Niels Olsen ^[1] ; Garcia Calich, Vera Lucia ^[1] ; Ochs, Hans D. ^{[6, 7]} ; Schimke, Lena F. ^[1] ; Jurisica, Igor ^{[8, 9, 10, 11, 12]} ; Condino-Neto, Antonio ^[1] ; Cabral-Marques, Otavio ^{[1, 2, 13]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Arts Sci & Humanities, Informat Syst, Sao Paulo - Brazil

^[4] Brown Univ, Dept Biostat, Providence, RI 02912 - USA

^[5] Brown Univ, Data Sci Initiat, Providence, RI 02912 - USA

^[6] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 - USA

^[7] Seattle Childrens Res Inst, Seattle, WA - USA

^[8] Univ Toronto, Dept Med Biophys, Toronto, ON - Canada

^[9] Univ Toronto, Dept Comp Sci, Toronto, ON - Canada

^[10] Slovak Acad Sci, Inst Neuroimmunol, Bratislava - Slovakia

^[11] Univ Toronto, Osteoarthrit Res Program, Div Orthoped Surg, Schroeder Arthrit Inst, UHN, Toronto, ON - Canada

^[12] Univ Toronto, Data Sci Discovery Ctr, Krembil Res Inst, UHN, Toronto, ON - Canada

^[13] Universal Sci Educ & Res Network USERN, Network Immun Infect Malignancy & Autoimmun NIIMA, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 OCT 13 2021.
• Web of Science Citations: 0

Abstract

Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention. (AU)

• FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Otávio Cabral Marques
• Support Opportunities: Regular Research Grants