Details

Autor(en) / Beteiligte

• Sacramento, Laís A
• Farias Amorim, Camila
• Campos, Taís M
• Saldanha, Maíra
• Arruda, Sérgio
• Carvalho, Lucas P
• Beiting, Daniel P
• Carvalho, Edgar M
• Novais, Fernanda O
• Scott, Phillip
• Rafati, Sima

Titel

NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis

Ist Teil von

• PLoS neglected tropical diseases, 2023-08, Vol.17 (8), p.e0011552-e0011552

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites' persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous leishmaniasis, we previously found that NKG2D plays a role in the ability of cytolytic CD8 T cells to promote disease in leishmanial lesions. Here, we investigated whether NKG2D plays a role in human disease. We found that NKG2D and its ligands were expressed within lesions from L. braziliensis-infected patients and that IL-15 and IL-1[beta] were factors driving NKG2D and NKG2D ligand expression, respectively. Blocking NKG2D reduced degranulation by CD8 T cells in a subset of patients. Additionally, our transcriptional analysis of patients' lesions found that patients who failed the first round of treatment exhibited higher expression of KLRK1, the gene coding for NKG2D, than those who responded to treatment. These findings suggest that NKG2D may be a promising therapeutic target for ameliorating disease severity in cutaneous leishmaniasis caused by L. braziliensis infection.