Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis

• Published in: Journal of fungi (Basel) Vol. 7; no. 8; p. 656
• Main Authors: Tan, Zhaohong, Mok, Michelle Meng Huang, Mar Soe, Win, Thamboo, Thomas Paulraj, Goh, Jessamine Geraldine, Sam, Qi Hui, Osato, Motomi, Ravikumar, Sharada, Chai, Louis Yi Ann
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 13.08.2021; MDPI
• Subjects: Candida albicans; Candidiasis; CD11b antigen; Complications; Cytokines; Dendritic cells; Experiments; Flow cytometry; Fungal infections; Immunological tolerance; Immunomodulation; Immunoregulation; Immunosuppressive agents; Inflammation; Interleukin 10; Interleukin 6; interleukin 6 blockade; Kidneys; Laboratory animals; Ligands; Lymphocytes T; Monoclonal antibodies; monoclonal antibody; Morbidity; Mortality; Transplants & implants; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon; United States > US; Singapore
• ISSN: 2309-608X; 2309-608X
• DOI: 10.3390/jof7080656

The existence of a hyperinflammatory state has been observed in patients with invasive fungal infections (IFI). It is being postulated whether morbidity from IFI may, in part, be a consequence of an unnecessarily prolonged or exaggerated proinflammatory immune response including interleukin 6 (IL-6) post-infection, in a host with dysregulated or compromised immunity. This, in turn, induces collateral host injury at the tissue and organ level, leading to adverse outcomes. Tocilizumab has become widely used as an immunomodulator in the treatment of inflammatory conditions. Here, we evaluated the use of tocilizumab to curb post-infective inflammatory flare in the setting of an in-vivo mouse model for invasive candidiasis. Following Candida infection, the tocilizumab-treated mice showed improved short-term survival compared with the saline-treated control mice. There was a reduced inflammatory response mounted by the host, coupled with reduced IL-6 but increased IL-10 levels. TNF-α and IFN-γ responses were not affected. Tocilizumab facilitated immune tolerance by selectively inducing IL-10, producing CD8α+ conventional dendritic cells (DCs) and peripheral T-regulatory cells, over CD11b+ conventional DCs and plasmacytoid DCs. We demonstrate here the sequelae from immunomodulatory manipulation and the basis whereby the use of monoclonal antibodies may be further explored in IFI.