PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response

Elizabeth, Mendoza-Coronel; Camacho-Sandoval, Rosa; Bonifaz, Laura C.; López-Vidal, Yolanda

doi:10.1016/j.tube.2010.11.008

Cited by 21 publications

(16 citation statements)

References 46 publications

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“…Elizabeth et al . also demonstrated that PD-L2 induction in dendritic cells exposed to Mycobacterium avium downregulated BCG-specific T-cell response27. These data suggested that the PD-1/PD-L pathway can exert an inhibitory role on macrophages function.…”

Section: Discussionmentioning

confidence: 70%

PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

Shen

Gao

Liu

et al. 2016

Sci Rep

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The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4+ T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1+CD4+ and PD-L1+CD4+ T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14+ monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4+ T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4+ T-cell-mediated immunity but also innate immunity.

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Section: Discussionmentioning

confidence: 70%

PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

Shen

Gao

Liu

et al. 2016

Sci Rep

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“…In human cells, Mabc-induced TNF-α production depends on the activation of the ERK1/2 and p38 MAPK pathways [36]. Further, M. avium infection prior to BCG resulted in the production of IL-10 in dendritic cells through the TLR2-p38 MAPK signaling pathway [42]. Our data are unique in demonstrating the critical role of JNK signaling in proinflammatory responses to Mmass in macrophage infection.…”

Section: Discussionmentioning

confidence: 87%

Mycobacterium massiliense Induces Inflammatory Responses in Macrophages Through Toll-Like Receptor 2 and c-Jun N-Terminal Kinase

Kim

Yoo³

et al. 2014

J Clin Immunol

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Mycobacterium massiliense (Mmass) is an emerging, rapidly growing mycobacterium (RGM) that belongs to the M. abscessus (Mabc) group, albeit clearly differentiated from Mabc. Compared with M. tuberculosis, a well-characterized human pathogen, the host innate immune response against Mmass infection is largely unknown. In this study, we show that Mmass robustly activates mRNA and protein expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in murine bone marrow-derived macrophages (BMDMs). Toll-like receptor (TLR)-2 and myeloid differentiation primary response gene 88 (MyD88), but neither TLR4 nor Dectin-1, are involved in Mmass-induced TNF-α or IL-6 production in BMDMs. Mmass infection also activates the mitogen-activated protein kinase (MAPKs; c-Jun N-terminal kinase (JNK), ERK1/2 and p38 MAPK) pathway. Mmass-induced TNF-α and IL-6 production was dependent on JNK activation, while they were unaffected by either the ERK1/2 or p38 pathway in BMDMs. Additionally, intracellular reactive oxygen species (ROS), NADPH oxidase-2, and nuclear factor-κB are required for Mmass-induced proinflammatory cytokine generation in macrophages. Furthermore, the S morphotype of Mmass showed lower overall induction of pro-inflammatory (TNF-α, IL-6, and IL-1β) and anti-inflammatory (IL-10) cytokines than the R morphotype, suggesting fewer immunogenic characteristics for this clinical strain. Together, these results suggest that Mmass-induced activation of host proinflammatory cytokines is mediated through TLR2-dependent JNK and ROS signaling pathways.

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“…Thus, we speculated that the regulatory function of TLR2 in schistosome infection is in part through selectively regulating PD-L2 expression. A study on Mycobacterium avium suggested that Mycobacterium avium induced high PD- L2expression on DCs, which was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway [32]. The MAPK family is composed of three major groups: p38, ERK1/2 and JNK1/2.…”

Section: Discussionmentioning

confidence: 99%

TLR2 Directing PD-L2 Expression Inhibit T Cells Response in Schistosoma japonicum Infection

et al. 2013

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Toll-like receptor 2 (TLR2) was shown to be an important immune receptor involved in the recognition of schistosome antigens, especially soluble egg antigen (SEA). In mice models with Schistosoma japonicum acute infection, we observed enhanced T cell-mediated immune responses in TLR2 knock out (TLR2−/−) mice compared with B6 mice. In Schistosoma japonicum chronic infection models, programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) expression as well as TLR2 expression gradually increased in B6 mice, while only PD-L2 expression significantly decreased in TLR2−/− mice. Meanwhile, Programmed Death 1(PD-1) expression on CD4+T cells was down-regulated in TLR2−/− mice after a large number of egg appeared. We also found that stimulation with schistosome antigens, especially SEA, could up-regulate PD-L2 expression on BMDCs in a TLR2-dependent manner in vitro. Schistosome antigens primed-BMDCs with impaired expression of TLR2 or PD-L2 could induce CD4+T cells to produce low level of IL-10 or high level of IFN-γ. Our results indicated that TLR2 signaling can direct PD-L2 expression on DCs, which binds to PD-1 mainly on CD4+T cells, to help inhibit T cells response in Schistosoma japonicum infection.

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PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response

Cited by 21 publications

References 46 publications

PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis

Mycobacterium massiliense Induces Inflammatory Responses in Macrophages Through Toll-Like Receptor 2 and c-Jun N-Terminal Kinase

TLR2 Directing PD-L2 Expression Inhibit T Cells Response in Schistosoma japonicum Infection

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