Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]

Publication Date:
2018-11-20
Publisher:
The American Association of Immunologists (AAI)
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Published by:
http://www.aai.org/
_version_ 1836399088927506432
autor Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
beschreibung 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.
citation_standardnr 6358763
datenlieferant ipn_articles
feed_id 333
feed_publisher The American Association of Immunologists (AAI)
feed_publisher_url http://www.aai.org/
insertion_date 2018-11-20
journaleissn 1550-6606
journalissn 0022-1767
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association of Immunologists (AAI)
quelle Journal of Immunology
relation http://www.jimmunol.org/cgi/content/short/201/11/3362?rss=1
search_space articles
shingle_author_1 Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
shingle_author_2 Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
shingle_author_3 Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
shingle_author_4 Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
shingle_catch_all_1 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
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.
Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_2 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
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.
Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_3 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
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.
Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_4 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
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.
Bunn, P. T., Montes de Oca, M., de Labastida Rivera, F., Kumar, R., Ng, S. S., Edwards, C. L., Faleiro, R. J., Sheel, M., Amante, F. H., Frame, T. C. M., Muller, W., Haque, A., Uzonna, J. E., Hill, G. R., Engwerda, C. R.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_title_1 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_2 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_3 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
shingle_title_4 Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
timestamp 2025-06-30T23:37:25.508Z
titel Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
titel_suche Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani [INFECTIOUS DISEASE AND HOST RESPONSE]
topic WW-YZ
uid ipn_articles_6358763