PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

Chiku, Vanessa Marim; Silva, Kathlenn Liezbeth Oliveira; Almeida, Breno Fernando Martins de; Venturin, Gabriela Lovizutto; Leal, Aline Aparecida Correa; Martini, Cristina; Eugênio, Flávia de Rezende; Santos, Paulo Sérgio Patto dos; Lima, Valéria Marçal Felix de

doi:10.1016/j.imbio.2016.03.007

Cited by 31 publications

(21 citation statements)

References 49 publications

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“…Recently it has been reported by our group and others that PD‐L1 is expressed on canine tumour cells and macrophages, both in vitro and in vivo . In dogs with visceral leishmaniasis, it was reported recently that PD‐1 signalling could induce T cell apoptosis …”

Section: Introductionmentioning

confidence: 93%

PD‐1 expression by canine T cells and functional effects of PD‐1 blockade

Coy

Caldwell

Chow

et al. 2017

Vet Comparative Oncology

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The co-inhibitory checkpoint molecule programmed death receptor 1 (PD-1) can trigger T cell functional exhaustion upon binding to its ligand PD-L1 expressed on tumour cells or macrophages. PD-1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD-1 were assessed for T cell binding and induction of functional activation. A total of 5-10% of CD4 T cells and 20-25% of CD8 T cells from healthy dogs expressed PD-1, and PD-1 expression was upregulated on T cells from dogs with cancer. Functionally, PD-1 antibodies significantly enhanced T-cell activation, as assessed by proliferation and interferon-gamma (IFN-) production. PD-1 antibodies also reversed T-cell suppression induced by canine soluble PD-L1 and by tumour cells and tumour explant fragments. These findings indicate that PD-1 antibodies have potential for use in cancer immunotherapy in dogs.

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Section: Introductionmentioning

confidence: 93%

PD‐1 expression by canine T cells and functional effects of PD‐1 blockade

Coy

Caldwell

Chow

et al. 2017

Vet Comparative Oncology

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“…Although several of the apoptosis-inducing mechanisms have been studied in the canine VL, [7,18,19], whether NO plays an important role in apoptosis and may contribute to the immunosuppression observed in canine VL has yet to be studied.…”

Section: Introductionmentioning

confidence: 99%

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis

Martini

Andrade

Almeida

et al. 2018

Comparative Immunology, Microbiology and Infectious Diseases

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Nitric oxide (NO) is involved in the death of the Leishmania parasite and regulation of apoptosis. We quantified the frequency of cells producing NO and its levels in the peripheral blood mononuclear cells (PBMC), leukocytes from spleen in Visceral Leishmaniasis (VL) symptomatic dogs and correlated NO levels with apoptosis and parasite load in the spleen. The percentage of NO+ cells and CD14+/NO+ was higher in PBMC and spleen cells in infected dogs than in controls. The levels of NO+ and CD14+/NO+ cells was higher in PBMC, but lower spleen of dogs infected than compared to control. Late apoptosis rates increased in PBMC and spleen of infected dogs compared to controls, and the NO levels and apoptosis not showed correlation. There was a positive correlation between the percentage of cells producing NO in the spleen and parasite load. The NO participates in the immune response in the canine VL, but it is not apoptosis inducer.

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“…To detect PD-1 expression, PBMCs were suspended in PBS containing 1% bovine serum albumin, 0.1% sodium azide and 20% fetal bovine serum, to block the Fc receptor (FcR). Cells were then mixed with either the PE-conjugated monoclonal anti-Human CD279 (PD-1) antibody [18,19] or an isotype control (BD Pharmigen, USA), according to the manufacturer instructions. Ten thousand events were acquired on the FL2 channel of a flow cytometer, and data analysis was performed as described above in the lymphoproliferation assay section (S2 Fig).…”

Section: Flow Cytometry Analysis For Labeling Pd-1 T-bet and Gata3 Imentioning

confidence: 99%

“…The inability of lymphocytes from dogs with leishmaniasis to proliferate and produce Th1 cytokines may be associated, at least in part, with increased PD-1 expression, which promotes apoptosis during the course of infection [18,19]. To assess whether interference in cytokine signaling could lead to reduced PD-1 expression in lymphocytes, PBMCs were cultured with or without SLA using combinations of recombinant canine proteins, or rcasIL-10R1 alone.…”

Section: Combinations Of Rcail12/rcail-2 and Rcail-12/rcail-15 Promotmentioning

confidence: 99%

“…In contrast, symptomatic dogs (susceptible to the infection) mount an exacerbated humoral immune response (Th2) that may be accompanied by increased production in of IL-10 [17]. In addition, susceptible dogs present increased expression of programmed cell death 1 (PD-1) and PD-1 ligands (PD-L1 and PDL-2), in splenic cells [18]. Such heightened expression of PD-1 and PD-1 ligands may suppress lymphoproliferation and alters the production of Th1 cytokines, contributing to the development of the disease [19].…”

Section: Introductionmentioning

confidence: 99%

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Combined in vitro IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

et al. 2020

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Domestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcaIL-12, rcaIL-2, rcaIL-15 and rcaIL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcaIL-12/rcaIL-2, rcaIL-12/rcaIL-15, rcaIL-12/rcasIL-10R1, rcaIL-15/rcaIL-7) or alone (rcasIL-10R1) to evaluate their immunomodulatory capacity in peripheral blood mononuclear cells (PBMCs) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoproliferative response. Further, the combinations rcaIL-12/rcaIL-2 and rcaIL-12/rcaIL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcaIL-12/rcasIL-10R1 induced IFN-γ and TNF-α production in PBMCs. Furthermore, the combination IL-12/IL-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcaIL-12 and rcaIL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the development of an effective treatment against CanL.

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PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

Cited by 31 publications

References 49 publications

PD‐1 expression by canine T cells and functional effects of PD‐1 blockade

PD‐1 expression by canine T cells and functional effects of PD‐1 blockade

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis

Combined in vitro IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

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