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Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10–Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani
| Content Provider | Scilit |
|---|---|
| Author | Bunn, Patrick T. de Oca, Marcela Montes de Labastida Rivera, Fabian Kumar, Rajiv Ng, Susanna S. Edwards, Chelsea L. Faleiro, Rebecca J. Sheel, Meru Amante, Fiona H. Frame, Teija C. M. Muller, Werner Haque, Ashraful Uzonna, Jude E. Hill, Geoffrey R. Engwerda, Christian R. |
| Copyright Year | 2018 |
| Description | The outcome of intracellular parasitic infection can be determined by the immunoregulatory activities of natural regulatory $CD4^{+}$ $Foxp3^{+}$ T (Treg) cells and the anti-inflammatory cytokine IL-10. These mechanisms protect tissue but can also suppress antiparasitic $CD4^{+}$ T cell responses. The specific contribution of these regulatory pathways during human parasitic diseases remains unclear. In this study, we investigated the roles of Treg cells and IL-10 during experimental visceral leishmaniasis caused by Leishmania donovani infection of C57BL/6 mice. We report only a limited contribution of Treg cells in suppressing antiparasitic immunity, but important roles in delaying the development of splenic pathology and restricting leukocyte expansion. We next employed a range of cell-specific, IL-10– and IL-10R–deficient mice and found these Treg cell functions were independent of IL-10. Instead, conventional $CD4^{+}$ T cells and dendritic cells were the most important cellular sources of IL-10, and the absence of IL-10 in either cell population resulted in greater control of parasite growth but also caused accelerated breakdown in splenic microarchitecture. We also found that T cells, dendritic cells, and other myeloid cells were the main IL-10–responding cells because in the absence of IL-10R expression by these cell populations, there was greater expansion of parasite-specific $CD4^{+}$ T cell responses associated with improved control of parasite growth. Again, however, there was also an accelerated breakdown in splenic microarchitecture in these animals. Together, these findings identify distinct, cell-specific, immunoregulatory networks established during experimental visceral leishmaniasis that could be manipulated for clinical advantage. |
| Ending Page | 3372 |
| Page Count | 11 |
| Starting Page | 3362 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1701582 |
| Journal | The Journal of Immunology |
| Issue Number | 11 |
| Volume Number | 201 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2018-12-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Specific Leishmania Donovani Leishmaniasis Caused Cell Responses |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
