Antigen recognition reinforces regulatory T cell mediated Leishmania major persistence

Romaniya Zayats, Zhirong Mou, Atta Yazdanpanah, Gaurav Gupta, Paul Lopez, Deesha Nayar, Wan H. Koh, Jude E. Uzonna () and Thomas T. Murooka ()
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Romaniya Zayats: University of Manitoba
Zhirong Mou: University of Manitoba
Atta Yazdanpanah: University of Manitoba
Gaurav Gupta: University of Manitoba
Paul Lopez: University of Manitoba
Deesha Nayar: University of Manitoba
Wan H. Koh: University of Manitoba
Jude E. Uzonna: University of Manitoba
Thomas T. Murooka: University of Manitoba

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Cutaneous Leishmania major infection elicits a rapid T cell response that is insufficient to clear residually infected cells, possibly due to the accumulation of regulatory T cells in healed skin. Here, we used Leishmania-specific TCR transgenic mice as a sensitive tool to characterize parasite-specific effector and immunosuppressive responses in vivo using two-photon microscopy. We show that Leishmania-specific Tregs displayed higher suppressive activity compared to polyclonal Tregs, that was mediated through IL-10 and not through disrupting cell-cell contacts or antigen presentation. In vivo expansion of endogenous Leishmania-specific Tregs resulted in disease reactivation that was also IL-10 dependent. Interestingly, lack of Treg expansion that recognized the immunodominant Leishmania peptide PEPCK was sufficient to restore robust effector Th1 responses and resulted in parasite control exclusively in male hosts. Our data suggest a stochastic model of Leishmania major persistence in skin, where cellular factors that control parasite numbers are counterbalanced by Leishmania-specific Tregs that facilitate parasite persistence.

Date: 2023
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DOI: 10.1038/s41467-023-44297-6

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