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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 .
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Dec 01; Vol. 201 (11), pp. 3362-3372. Date of Electronic Publication: 2018 Oct 24. - Publication Year :
- 2018
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Abstract
- The outcome of intracellular parasitic infection can be determined by the immunoregulatory activities of natural regulatory CD4 <superscript>+</superscript> Foxp3 <superscript>+</superscript> T (Treg) cells and the anti-inflammatory cytokine IL-10. These mechanisms protect tissue but can also suppress antiparasitic CD4 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
CD4 Antigens metabolism
Cells, Cultured
Female
Forkhead Transcription Factors metabolism
Humans
Immunomodulation
Mice
Mice, Inbred C57BL
Models, Animal
Interleukin-10 metabolism
Leishmania donovani physiology
Leishmaniasis, Visceral immunology
Spleen immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 201
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 30355785
- Full Text :
- https://doi.org/10.4049/jimmunol.1701582