Abstract
Leishmaniasis is a neglected disease, for which current treatment presents numerous issues. Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The roles of the programmed death-1 (PD-1) receptor on lymphocytes and its ligand (PD-L1) on antigen-presenting cells have been well studied in tumor and other infection models; but little is known about their roles in non-healing cutaneous leishmaniasis. In this study, we observed that L. amazonensis induced PD-1 expression on both CD4+ and CD8+ T cells and PD-L1 on dendritic cells on BALB/c mice. We tested the therapeutic potential of anti-PD-1 and anti-PD-L1 monoclonal antibodies (MoAbs) against a non-healing L. amazonensis infection in BALB/c mice, and that anti-PD-1 and anti-PD-L1 treatment significantly increased IFN-γ-producing CD4+ and CD8+ T cells, respectively. Compared with infection controls, mice treated with anti-PD-1 and anti-PD-L1, but not anti-PD-L2, displayed bigger lesions with significantly lower parasite loads. Treatment did not affect anti-Leishmania antibody (IgM, IgG, IgG1 and IgG2a) or IL-10 production, but anti-PD-1 treatment reduced both IL-4 and TGF-β production. Together, our results highlight the therapeutic potential of an anti-PD-1-based treatment in promoting the reinvigoration of T cells for the control of parasite burden.
Highlights
Leishmaniasis is a neglected disease, for which current treatment presents numerous issues
Here we investigate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) upon L. amazonensis infection in BALB/c mice, and evaluate the use of monoclonal antibodies (MoAbs) against PD-1 and PD-L1 as therapies for the severe form of leishmaniasis caused by L. amazonensis
As the percentage and number of PD-1+CD8+ T cells were increased in L. amazonensis infection (Fig. 1), we examined whether the IFN-γ production could be affected in the CD8+ T cells lacking PD-1 (PD-1−CD8+) during MoAb treatment
Summary
Leishmaniasis is a neglected disease, for which current treatment presents numerous issues. We tested the therapeutic potential of anti-PD-1 and anti-PD-L1 monoclonal antibodies (MoAbs) against a non-healing L. amazonensis infection in BALB/c mice, and that anti-PD-1 and anti-PD-L1 treatment significantly increased IFN-γ-producing CD4+ and CD8+ T cells, respectively. Liang and colleagues have reported that L. mexicana-infected PD-L1−/− mice have increased production of IFN-γ in T cells, reduced disease progression, and greater control of the parasite load when compared with infected wild-type (WT) mice. In PD-L2−/− mice, there was an increased lesion size and increased parasite load compared to WT mice, which implies there are differing roles for PD-L1 and PD-L2 in regulating IFN-γ production These results suggest the participation only of PD-L1 in the T exhaustion process during L. mexicana infection[15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
