Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis
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)...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/7/8/656 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zhaohong Tan |
| collection | DOAJ |
| description | 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 <i>Candida</i> 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. |
| first_indexed | 2024-03-10T08:40:54Z |
| format | Article |
| id | doaj.art-5049391d15ec4ecd9a941c0a257a31bf |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T08:40:54Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-5049391d15ec4ecd9a941c0a257a31bf2023-11-22T08:17:25ZengMDPI AGJournal of Fungi2309-608X2021-08-017865610.3390/jof7080656Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive CandidiasisZhaohong Tan0Michelle Meng Huang Mok1Win Mar Soe2Thomas Paulraj Thamboo3Jessamine Geraldine Goh4Qi Hui Sam5Motomi Osato6Sharada Ravikumar7Louis Yi Ann Chai8Department of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeCancer Science Institute of Singapore, National University of Singapore, Singapore 117599, SingaporeDepartment of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeDepartment of Pathology, National University of Singapore, Singapore 117596, SingaporeDepartment of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeDepartment of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeCancer Science Institute of Singapore, National University of Singapore, Singapore 117599, SingaporeDepartment of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeDepartment of Medicine, Division of Infectious Diseases, National University Health System, Singapore 119228, SingaporeThe 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 <i>Candida</i> 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.https://www.mdpi.com/2309-608X/7/8/656<i>Candida albicans</i>interleukin 6 blockadeinflammationimmunomodulationmonoclonal antibody |
| spellingShingle | 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 Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis Journal of Fungi <i>Candida albicans</i> interleukin 6 blockade inflammation immunomodulation monoclonal antibody |
| title | Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis |
| title_full | Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis |
| title_fullStr | Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis |
| title_full_unstemmed | Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis |
| title_short | Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis |
| title_sort | tocilizumab induces il 10 mediated immune tolerance in invasive candidiasis |
| topic | <i>Candida albicans</i> interleukin 6 blockade inflammation immunomodulation monoclonal antibody |
| url | https://www.mdpi.com/2309-608X/7/8/656 |
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