Role of myeloid-derived suppressor and Th17/Treg cells in post-COVID-19 Rhino-Orbital mucormycosis cases
Creators: name: Singh, Praveen Kumar
name: Rai, Gargi
name: Das, Shukla
name: Ansari, Mohammad Ahmad
name: Ashgar, Rnda I.
name: Gupta, Neelima
name: Arora, Vipin
name: Sharma, Sonal
name: Dar, Sajad Ahmad
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Cancer
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: <b>Background:</b> Rhino-Orbital-Cerebral Mucormycosis (ROCM) cases increased sharply in India during the second COVID-19 wave. Due to uncontrolled hyperglycemia, prolonged steroid use, and high ferritin levels, the immune system was dysregulated throughout this surge. <b>Methods:</b> Our study examined post-COVID-19 ROCM patients’ T regulatory cell (Treg), T helper 17 cell (Th17) and Myeloid derived suppressor cell (MDSC) levels before and after three months of treatment. T cell activation and MDSC profile were measured in peripheral blood from 20 post-COVID-19 mucormycosis patients and 20 age-matched controls. <b>Results:</b> Compared to controls, cases had significantly greater Th17 cells (CD4<sup>+</sup>IL-23R<sup>+</sup>) before and after treatment (<i>p</i> &lt; 0.05), with no significant change between pre- and post-treatment. In pretreatment cases, Treg cells (CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>) were lower than controls, but dramatically increased (<i>p</i> &lt; 0.05) following treatment. Further, these patients had significantly higher rates of monocytic (m) MDSCs (CD14<sup>+</sup>HLA-DR<sup>low/-</sup>) compared to healthy persons (<i>p</i> &lt; 0.05). Interestingly, after three months of treatment, mMDSC levels dropped to levels similar to healthy controls. Similarly, ROCM patients had higher levels of granulocytic (g) MDSCs (HLA-DR<sup>low/-</sup>CD33<sup>+</sup>CD11b<sup>+</sup>CD66<sup>+</sup>) than healthy controls, although these levels normalized after three months. Patients had considerably greater expression levels of RORγt, TGF-β, and IL-10 mRNA before therapy compared to healthy controls. FoxP3 and Arg-1 mRNA expression was lower in pretreatment patients than in healthy people. After treatment, these individuals’ IL-10, FoxP3, and Arg-1 mRNA expression increased. <b>Conclusion:</b> MDSCs may play a role in mucormycosis immunological dysregulation, suggesting that restoring balance may improve patient outcomes. Post-COVID ROCM patients had more IL-23R<sup>+</sup> Th17 cells than CD4<b><i><sup>+</sup></i></b>CD25<b><i><sup>+</sup></i></b>Treg cellsMonocytic MDSC were elevated in ROCM patients, pretreatment, than healthy controlsAn immune dysregulation mechanism involving MDSC in post-COVID ROCM is evident Post-COVID ROCM patients had more IL-23R<sup>+</sup> Th17 cells than CD4<b><i><sup>+</sup></i></b>CD25<b><i><sup>+</sup></i></b>Treg cells Monocytic MDSC were elevated in ROCM patients, pretreatment, than healthy controls An immune dysregulation mechanism involving MDSC in post-COVID ROCM is evident