دورية أكاديمية
Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy.
| العنوان: | Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy. |
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| المؤلفون: | Preite NW; Institute of Science and Technology, Federal University of São Paulo, São José dos Campos, São Paulo, Brazil., Kaminski VL; Institute of Science and Technology, Federal University of São Paulo, São José dos Campos, São Paulo, Brazil., Borges BM; Institute of Science and Technology, Federal University of São Paulo, São José dos Campos, São Paulo, Brazil., Calich VLG; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Loures FV; Institute of Science and Technology, Federal University of São Paulo, São José dos Campos, São Paulo, Brazil. |
| المصدر: | Frontiers in immunology [Front Immunol] 2023 Jan 26; Vol. 14, pp. 1039244. Date of Electronic Publication: 2023 Jan 26 (Print Publication: 2023). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Paracoccidioidomycosis* , Myeloid-Derived Suppressor Cells*, Mice ; Animals ; Th17 Cells/pathology ; Mice, Inbred C57BL ; Lung |
| مستخلص: | Previous studies on paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America, revealed that host immunity is tightly regulated by several suppressive mechanisms mediated by tolerogenic plasmacytoid dendritic cells, the enzyme 2,3 indoleamine dioxygenase (IDO-1), and regulatory T-cells (Tregs). IDO-1 orchestrates local and systemic immunosuppressive effects through the recruitment and activation of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells possessing a potent ability to suppress T-cell responses. However, the involvement of MDSCs in PCM remains uninvestigated. The presence, phenotype, and immunosuppressive activity of MDSCs were evaluated at 96 h, 2 weeks, and 8 weeks of pulmonary infection in C57BL/6 mice. Disease severity and immune responses were assessed in MDSC-depleted and nondepleted mice using an anti-Gr1 antibody. Both monocytic-like MDSCs (M-MDSCs) and polymorphonuclear-like MDSCs (PMN-MDSCs) massively infiltrated the lungs during Paracoccidioides brasiliensis infection. Partial reduction of MDSC frequency led to a robust Th1/Th17 lymphocyte response, resulting in regressive disease with a reduced fungal burden on target organs, diminishing lung pathology, and reducing mortality ratio compared with control IgG2b-treated mice. The suppressive activity of MDSCs on CD4 and CD8 T-lymphocytes and Th1/Th17 cells was also demonstrated in vitro using coculture experiments. Conversely, adoptive transfer of MDSCs to recipient P. brasiliensis -infected mice resulted in a more severe disease. Taken together, our data showed that the increased influx of MDSCs into the lungs was linked to more severe disease and impaired Th1 and Th17 protective responses. However, protective immunity was rescued by anti-Gr1 treatment, resulting in a less severe disease and controlled tissue pathology. In conclusion, MDSCs have emerged as potential target cells for the adjuvant therapy of PCM. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Preite, Kaminski, Borges, Calich and Loures.) |
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| فهرسة مساهمة: | Keywords: MDSC (myeloid-derived suppressor cell); fungal infection; immunoregulation; lung immune cells; paracoccidioidomycosis (PCM) |
| تواريخ الأحداث: | Date Created: 20230213 Date Completed: 20230214 Latest Revision: 20230217 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9909482 |
| DOI: | 10.3389/fimmu.2023.1039244 |
| PMID: | 36776848 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2023.1039244 |