Histidine acid phosphatase domain-containing protein from Haemonchus contortus is a stimulatory antigen for the Th1 immune response of goat PBMCs

Wen, Zhaohai; Zhang, Zhaoying; Aimulajiang, Kalibixiati; Aleem, Muhammad Tahir; Feng, Jiajun; Meng, Liang; Lu, Mingmin; Xu, Lixin; Song, Xiaoling; Li, Xiangrui; Ren, Yan

doi:10.1186/s13071-022-05411-7

Cited by 5 publications

(4 citation statements)

References 57 publications

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“…First, TRI-zol reagent was used to isolate total RNA from adult worms (Vazyme Biotech Co., Ltd., Nanjing, China). Next, the HiScript III First Strand cDNA Synthesis Kit was used to synthesize 1 μg of RNA into complementary DNA (cDNA) [ 32 , 33 ]. The Ts-MAPRC2 gene in T. spiralis was cloned and recombinant protein (rTs-MAPRC2) was produced using the method given in our previous research [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Aleem,

Wen,

et al. 2023

Vaccines

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Trichinella spiralis (T. spiralis), a nematode parasite, is the major cause of Trichinellosis, a zoonotic disease. A key role of MAPR in the reproductive system is to maintain pregnancy. Previous studies found that antihormone drug design and vaccine therapy of recombinant protein (rTs-MAPRC2) control T. spiralis infection. The current study investigates the inhibitory effects of different ratios of antibodies against Ts-MAPRC2 on the development of muscle larvae (ML) and newborn larvae (NBL). First, we performed indirect immunofluorescence assays and examined the effects of rTs-MAPRC2-Ab on ML and NBL in vitro as well as in vivo. Afterward, siRNA-Ts-MAPRC2 was transfected into T. spiralis muscle larvae. Following that, Ts-MAPRC2 protein was detected by Western Blotting, and mRNA levels were determined by qPCR. We also assessed whether siRNA-treated NBLs were infective by analyzing muscle larvae burden (MLs). Our results showed that rTs-MAPRC2-Ab greatly inhibited the activity of the Ts-MAPRC2 in ML and NBL of T. spiralis and rTs-MAPRC2-Ab reduced larval infectivity and survival in the host in a dose-dependent manner (1:50, 1:200, 1:800 dilutions). Furthermore, siRNA-Ts-MAPRC2 effectively silenced the Ts-MAPRC2 gene in muscle larvae (ML) in vitro, as well as in newborn larvae (NBL) of T. spiralis in vivo. In addition, siRNA-Ts-MAPRC2 (siRNA180, siRNA419, siRNA559) reduced host larval survival and infectivity significantly. This study, therefore, suggests that Ts-MAPRC2 might be a novel molecular target useful in the development of vaccines against T. spiralis infection.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Aleem,

Wen,

et al. 2023

Vaccines

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“…Cell proliferation was assayed with the Cell Counting Kit-8 (CCK-8, Beyotime) with reference to previous studies ( 26 ). Briefly, freshly isolated PBMCs (concentration of 1×10 6 /mL) were homogenously added to 96-well cell culture plates at 100 μL per well.…”

Section: Methodsmentioning

confidence: 99%

Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus

Wen

Zhang²,

Feng³

et al. 2022

Front. Immunol.

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Haemonchus contortus is an important parasitic nematode of ruminants. Previous studies showed that H. contortus escape the immunity through complex mechanisms, including releasing excretory/secretory proteins (ESPs) to modulate the host immune response. However, the detailed mechanism through which H. contortus excretory/secretory proteins (HcESPs) promote immune evasion remains unknown. In the present study, we demonstrated that HcESPs inhibit the adaptive immune response of goats including downregulation of immune cell antigen presentation, upregulation of immune checkpoint molecules, activation of the STAT3/PD-L1 pathway, and activation of immunosuppressive regulatory T (Treg) cells. Furthermore, HcESPs reversed the LPS-induced upregulation of pro-inflammatory mediators in PBMCs by inhibiting the TLR4/NF-κB/MAPKs/NLRP3 signaling pathway. Our study provides a better understanding of the evasion mechanisms for H. contortus, which could be helpful in providing an alternative way to prevent the infection of this parasite.

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“…Next, the HiScript III First Strand cDNA Synthesis Kit was used to synthesize 1 µg of RNA into complementary DNA (cDNA) [32,33]. The Ts-MAPRC2 gene in T. spiralis was cloned and recombinant protein (rTs-MAPRC2) was produced using the method given in our previous research [24].…”

Section: Molecular Cloning Of Ts-maprc2 and Rts-maprc2 Protein Produc...mentioning

confidence: 99%

Inhibition of Trichinella spiralis Membrane‐Associated Progesterone Receptor (MAPR) Results in the Reduction of Worm Burden

Aleem¹,

Wen²,

Yu³

et al. 2023

Preprint

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Trichinella spiralis (T. spiralis), a nematode parasite, is the major cause of Trichinellosis, a zoonotic disease. A key role of MAPR in the reproductive system is to maintain pregnancy. Previous studies found antihormone (P4 and RU486) drug design and vaccine therapy of recombinant protein (rTs-MAPRC2) to control T. spiralis infection. The current study investigates the inhibitory effects of different ratios of antibody against Ts-MAPRC2 on the development of muscle larvae (ML) and newborn larvae (NBL). First, we performed indirect immunofluorescence assays (IIFA) and examined the effects of rTs-MAPRC2-Ab on ML and NBL in vitro as well as in vivo. After-ward, siRNA-Ts-MAPRC2 was transfected into T. spiralis muscle larvae. Following that, Ts-MAPRC2 protein was detected by Western Blotting and mRNA levels were determined by qPCR. Also, we assessed whether siRNA-treated NBLs were infective by analyzing muscle larvae burden (MLs). Our Result showed rTs-MAPRC2-Ab greatly inhibited the activity of the Ts-MAPRC2 gene in ML and NBL of T. spiralis. rTs-MAPRC2-Ab reduced larval infectivity and survival in the host in a dose-dependent manner (1:50, 1:200, 1:800 dilutions). Further, siR-NA-Ts-MAPRC2 effectively silenced the Ts-MAPRC2 gene in muscle larvae (ML) by in vitro, as well as in new-born larvae (NBL) of T. spiralis by in vivo. In addition, siRNA-Ts-MAPRC2 (siR-NA180, siRNA419, siRNA559) reduced host larval survival and infectivity significantly. The effect of siRNA on larval development, survival, and infectivity was significantly reduced when the Ts-MAPRC2 gene was knocked down. This study, therefore, suggests that Ts-MAPRC2 might be a novel molecular target that might be useful in the development of vaccines against T. spiralis infection.

show abstract

Histidine acid phosphatase domain-containing protein from Haemonchus contortus is a stimulatory antigen for the Th1 immune response of goat PBMCs

Cited by 5 publications

References 57 publications

Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus

Inhibition of Trichinella spiralis Membrane‐Associated Progesterone Receptor (MAPR) Results in the Reduction of Worm Burden

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