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<p><i>Leishmania amazonensis</i> is an etiological agent of diffuse cutaneous leishmaniasis in South America. In murine models, dysfunctional expansion of effector T cells and Th1 response exhaustion are linked to pathogenesis, while regulatory T cells (Tregs) promote lesion resolution. This study examined the roles of PD-1 and PD-L1 in the immunopathogenesis of <i>L. amazonensis</i> infection in C57BL/6 mice. We found a significant increase in PD-1 and PD-L1 expression in infected tissues, correlating with increased PD-L1<sup>+</sup>CD11c<sup>+</sup> dendritic cells (DCs) and PD-1<sup>+</sup>CD4<sup>+</sup> T cells in draining lymph nodes. Infection of bone marrow-derived DCs (BMDCs) with promastigotes and amastigotes revealed that PD-L1 expression was induced by mTOR, partially by STAT3, PI3K, and MAPK. Infected BMDCs <i>in vitro</i> inhibited Th1 cell expansion compared to non-infected BMDCs. <i>In vivo</i> experiments showed that PD-L1<sup>−/−</sup> mice exhibited increased Th1 responses, reduced lesion sizes, and lower parasite loads. These results suggest a non-protective role for PD-1/PD-L1 signaling in regulating local immune responses during <i>L. amazonensis</i> infection, providing new insights into immune regulation in New World cutaneous leishmaniasis.</p>

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Leishmania amazonensis infection induces PD-L1 expression on dendritic cells and impairs Th1 responses in vitro and in vivo

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月29日

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  • Herbert Leonel de Matos Guedes,
  • Alessandra Marcia da Fonseca-Martins,
  • Yuejin Liang,
  • Eric D. Carlsen,
  • Calvin A. Henard,
  • Irina V. Pinchuk,
  • Lynn Soong

摘要

Leishmania amazonensis is an etiological agent of diffuse cutaneous leishmaniasis in South America. In murine models, dysfunctional expansion of effector T cells and Th1 response exhaustion are linked to pathogenesis, while regulatory T cells (Tregs) promote lesion resolution. This study examined the roles of PD-1 and PD-L1 in the immunopathogenesis of L. amazonensis infection in C57BL/6 mice. We found a significant increase in PD-1 and PD-L1 expression in infected tissues, correlating with increased PD-L1+CD11c+ dendritic cells (DCs) and PD-1+CD4+ T cells in draining lymph nodes. Infection of bone marrow-derived DCs (BMDCs) with promastigotes and amastigotes revealed that PD-L1 expression was induced by mTOR, partially by STAT3, PI3K, and MAPK. Infected BMDCs in vitro inhibited Th1 cell expansion compared to non-infected BMDCs. In vivo experiments showed that PD-L1−/− mice exhibited increased Th1 responses, reduced lesion sizes, and lower parasite loads. These results suggest a non-protective role for PD-1/PD-L1 signaling in regulating local immune responses during L. amazonensis infection, providing new insights into immune regulation in New World cutaneous leishmaniasis.