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

Autor: Zhaohong Tan, Michelle Meng Huang Mok, Win Mar Soe, Thomas Paulraj Thamboo, Jessamine Geraldine Goh, Qi Hui Sam, Motomi Osato, Sharada Ravikumar, Louis Yi Ann Chai
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Fungi, Vol 7, Iss 8, p 656 (2021)
Druh dokumentu: article
ISSN: 2309-608X
DOI: 10.3390/jof7080656
Popis: 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.
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