Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes.
Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes.
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DOI：
10.1371/journal.ppat.1006349
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发表时间：
2017-04
期刊：
影响因子：
6.7
通讯作者：
Scott P
中科院分区：
文献类型：
--
作者：
Glennie ND;Volk SW;Scott P
Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. Cutaneous leishmaniasis is a neglected tropical disease, causing significant worldwide morbidity. There is no vaccine for this infection, in part because of our limited understanding of the memory T cells that might contribute to immunity. We previously discovered that a population of skin-resident memory CD4+ T cells that develop in immune mice enhances the protective immune response against leishmania parasites. Here we show that these skin-resident T cells mediate protection within the first three days of infection. This protection was dependent upon the recruitment of inflammatory monocytes to the challenge site, which reduced the parasite burden in a nitric oxide and reactive oxygen species dependent manner. A series of experiments including blockade of cell recruitment from the blood to the lesions, skin grafts, and parabiosis demonstrated that circulating effector T cells do not contribute to this early protection. Together, these results emphasize that skin-resident CD4+ T cells play a primary role in controlling parasites immediately after challenge, which not only indicates the importance of generating these cells in a vaccine, but also expands our understanding of the functions of skin-resident CD4+ T cells.
