Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection

Zhang, Yumei; Wu, Yuankui; Liu, Hua; Gong, Weiming; Hu, Yuan; Shen, Yujuan; Cao, Jianping

doi:10.1186/s13071-021-05006-8

Cited by 14 publications

(11 citation statements)

References 46 publications

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“…With the progression of schistosomiasis, the expression of Programmed Cell Death Protein 1 (PD‐1) on T follicular helper (Tfh) cells and PD‐L1 from myeloid‐derived suppressor cells increases. Granulocytic myeloid‐derived suppressor cells might regulate Tfh cells through the PD‐1/PD‐L1 pathway 15 . A recent study has shown that PD‐1‐deficient Tregs expressed larger amounts of adenosine receptors CD39 and CD73 that were crucial for Treg‐mediated immunosuppression 16 …”

Section: Introductionmentioning

confidence: 99%

“…Granulocytic myeloidderived suppressor cells might regulate Tfh cells through the PD-1/PD-L1 pathway. 15 A recent study has shown that PD-1-deficient Tregs expressed larger amounts of adenosine receptors CD39 and CD73 that were crucial for Tregmediated immunosuppression. 16 Sj16 was first identified from S. japonicum as a homolog of Sm16 from S. mansoni, 17 and was reported to be upregulated in the parasite stages of cercariae, eggs, miracidia, sporocysts, and lung-stage schistosomula.…”

Section: Introductionmentioning

confidence: 99%

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CRISPR/Cas9‐mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host‐to‐egg immune response

et al. 2022

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Schistosomiasis is an important, neglected tropical disease. Schistosoma japonicum can evade host attacks by regulating the host's immunity, causing continuous infection. However, interactions between the host's immune system and S. japonicum are unclear. Our previous research found that the Sj16 protein isolated from S. japonicum has an anti-inflammatory effect in the host. However, the role of Sj16 in the regulation of host immunity in S. japonicum infection is not clear.Here, we applied the CRISPR/Cas9 technique to knockout Sj16 in S. japonicum eggs and investigated the effect of Sj16 in regulating host immunity. We found egg viability decreased after Sj16 knockout. In addition, we found granulomatous inflammation increased, the T-cell immune response enhanced and the immune microenvironment changed in mice model injected with Sj16-knockout eggs by tail vein. These findings suggested that S. japonicum could regulate host immunity through Sj16 to evade the host immune attack and cause continuous infection. In addition, we confirmed the application of CRISPR/Cas9-mediated gene reprogramming for functional genomics in S. japonicum.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9‐mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host‐to‐egg immune response

et al. 2022

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“…Furthermore, the proportion and activation of CD4 + T cells and CD8 + T cells decreased significantly with the increase of MDSCs at 6-7 weeks after infection (Fig 2). These results suggested that pulmonary CD11b + Gr1 + cells from S. japonicum-infected mice have a suppressive function and are considered to be MDSCs [16,35].…”

Section: Discussionmentioning

confidence: 91%

“…These results suggested that pulmonary CD11b + Gr1 + cells from S . japonicum -infected mice have a suppressive function and are considered to be MDSCs [ 16 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

TLR7 controls myeloid-derived suppressor cells expansion and function in the lung of C57BL6 mice infected with Schistosoma japonicum

Zhou

Zhu²,

Mo³

et al. 2022

PLoS Negl Trop Dis

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Toll-like receptors (TLRs) play an important role in the induction of innate and adaptive immune responses against Schistosoma japonicum (S. japonicum) infection. However, the role of Toll-like receptor 7 (TLR7) in the mouse lung during S. japonicum infection and the myeloid-derived suppressor cells (MDSCs) affected by the absence of TLR7 are not clearly understood. In this study, the results indicated that the MDSCs were accumulated and the proportion and activation of CD4+ and CD8+ T cells were decreased in the lung of mice at 6–7 weeks after S. japonicum infection. Then, the expression of TLR7 was detected in isolated pulmonary MDSCs and the results showed that the expression of TLR7 in MDSCs was increased after infection. Furthermore, TLR7 agonist R848 could down-regulate the induction effect of the soluble egg antigen (SEA) on pulmonary MDSCs in vitro. Meanwhile, TLR7 deficiency could promote the pulmonary MDSCs expansion and function by up-regulating the expression of PD-L1/2 and secreting of IL-10 in the mice infected with S. japonicum. Mechanistic studies revealed that S. japonicum infection and the antigen effects are mediated by NF-κB signaling. Moreover, TLR7 deficiency aggravates S. japonicum infection-induced damage in the lung, with more inflammatory cells infiltration, interstitial dilatation and granuloma in the tissue. In summary, this study indicated that TLR7 signaling inhibits the accumulation and function of MDSCs in S. japonicum infected mouse lung by down-regulating the expression of PD-L1/2 and secreting of IL-10, via NF-κB signaling.

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“…A more recent study by Zhang et al (2021) showed that Myeloid-Derived-Suppressor-Cells (MDSC) in S. japonicum infected murine models were able to regulate the T-follicular -helper cells (Tfh-cells) proliferation via PD-1/PD-L1 axis (62). The authors reported that SEA and SWA could induce the generation of Tfh-cells in which the PD-1 expression rises along with PD-L1 in MDSC.…”

Section: Pd-l1 In Infectionsschistosomiasis Casementioning

confidence: 99%

Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma – There’s room for Immune Checkpoint Blockage?

Madureira

2022

Front. Immunol.

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Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is a carcinogen type 1 since 1994. It is strongly associated with bladder squamous-cell carcinoma in endemic regions, where it accounts for 53-69% of bladder-carcinoma cases. This histological subtype is associated with chronic inflammation being more aggressive and resistant to conventional chemo and radiotherapy. Immune-Checkpoint-Blockage (ICB) therapies targeting the Programmed-Cell-Death-Protein-1(PD-1)/Programmed-Cell-Death-Ligand-1(PD-L1) axis showed considerable success in treating advanced bladder urothelial carcinoma. PD-L1 is induced by inflammatory stimuli and expressed in immune and tumor cells. The binding of PD-L1 with PD-1 modulates immune response leading to T-cell exhaustion. PD-L1 presents in several isoforms and its expression is dynamic and can serve as its expression acts as a companion marker for patients’ eligibility, allowing the identification of positive tumors that are more likely to respond to ICB therapy. The high PD-L1 expression in bladder-urothelial-carcinoma and squamous-cell carcinoma may affect further ICB-therapy application and outcomes. In general, divergent histologies are ineligible for therapy. These treatments are expensive and prone to auto-immune side effects and resistance. Thus, biomarkers capable of predicting therapy response are needed. Also, the PD-L1 expression assessment still needs refinement. Studies focused on squamous cell differentiation associated with S. haematobium remain scarce. Furthermore, in low and middle-income-regions, where schistosomiasis is endemic, SCC biomarkers are needed. This mini-review provides an overview of the current literature regarding PD-L1 expression in bladder-squamous-cell-carcinoma and schistosomiasis. It aims to pinpoint future directions, controversies, challenges, and the importance of PD-L1 as a biomarker for diagnosis, disease aggressiveness, and ICB-therapy prognosis in bladder-schistosomal-squamous-cell carcinoma.

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Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection

Cited by 14 publications

References 46 publications

CRISPR/Cas9‐mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host‐to‐egg immune response

CRISPR/Cas9‐mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host‐to‐egg immune response

TLR7 controls myeloid-derived suppressor cells expansion and function in the lung of C57BL6 mice infected with Schistosoma japonicum

Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma – There’s room for Immune Checkpoint Blockage?

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