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The absence of CCR7 results in dysregulated monocyte migration and immunosuppression facilitating chronic cutaneous leishmaniasis
Citation
Kling, JC and Mack, M and Korner, H, The absence of CCR7 results in dysregulated monocyte migration and immunosuppression facilitating chronic cutaneous leishmaniasis, PLOS One, 8, (10) Article e79098. ISSN 1932-6203 (2013) [Refereed Article]
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Copyright Statement
Copyright 2013 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1371/journal.pone.0079098
Abstract
The protozoan parasite Leishmania major causes cutaneous lesions to develop at the site of infection, which are resolved with a strong Th1 immune response in resistant hosts, such as C57BL/6 mice. In contrast, the lesions ulcerate in susceptible hosts which display a Th2 response, such as BALB/c mice. The migration of cells in the immune response to L. major is regulated by chemokines and their receptors. The chemokine receptor CCR7 is expressed on activated DCs and naïve T cells, allowing them to migrate to the correct micro-anatomical positions within secondary lymphoid organs. While there have been many studies on the function of CCR7 during homeostasis or using model antigens, there are very few studies on the role of CCR7 during infection. In this study, we show that B6.CCR7(-/-) mice were unable to resolve the lesion and developed a chronic disease. The composition of the local infiltrate at the lesion was significantly skewed toward neutrophils while the proportion of CCR2(+) monocytes was reduced. Furthermore, a greater percentage of CCR2(+) monocytes expressed CCR7 in the footpad than in the lymph node or spleen of B6.WT mice. We also found an increased percentage of regulatory T cells in the draining lymph node of B6.CCR7(-/-) mice throughout infection. Additionally, the cytokine milieu of the lymph node showed a Th2 bias, rather than the resistant Th1 phenotype. This data shows that CCR7 is required for a protective immune response to intracellular L. major infection.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Immunology |
| Research Field: | Immunology not elsewhere classified |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Kling, JC (Miss Jessica Kling) |
| UTAS Author: | Korner, H (Professor Heinrich Korner) |
| ID Code: | 87368 |
| Year Published: | 2013 |
| Web of Science® Times Cited: | 10 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2013-11-13 |
| Last Modified: | 2018-12-14 |
| Downloads: | 220 View Download Statistics |
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