Cryptosporidium parvum downregulates miR-181d in HCT-8 cells via the p50-dependent TLRs/NF-κB pathway

Feng, Ruiying; Niu, Ziwen; Zhang, Xiaotian; Hou, Wenyan; Zhang, Yingying; Jian, Fuchun; Ning, Changshen; Zhang, Longxian; Wang, Rongjun

doi:10.1016/j.vetpar.2022.109710

Cited by 9 publications

(2 citation statements)

References 33 publications

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“…Previous studies suggested that activation of NF-κB inhibited infected epithelial cell apoptosis and facilitated parasite survival [ 37 ]. Activation of the TLR/NF-ĸB signaling pathway in host cells may trigger the transcriptional regulation of miRNA genes [ 38 , 39 ]. However, it is unclear whether the NF-κB signaling pathway can regulate the expression of miR-3976 and whether NF-κB is involved in miR-3976 targeting of BCL2A1 to regulate cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection

Sun

Xie

et al. 2023

Parasites Vectors

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Background Cryptosporidium is second only to rotavirus as a cause of moderate-to-severe diarrhea in young children. There are currently no fully effective drug treatments or vaccines for cryptosporidiosis. MicroRNAs (miRNAs) are involved in regulating the innate immune response to Cryptosporidium parvum infection. In this study, we investigated the role and mechanism of miR-3976 in regulating HCT-8 cell apoptosis induced by C. parvum infection. Methods Expression levels of miR-3976 and C. parvum burden were estimated using real-time quantitative polymerase chain reaction (RT-qPCR) and cell apoptosis was detected by flow cytometry. The interaction between miR-3976 and B-cell lymphoma 2-related protein A1 (BCL2A1) was studied by luciferase reporter assay, RT-qPCR, and western blotting. Results Expression levels of miR-3976 were decreased at 8 and 12 h post-infection (hpi) but increased at 24 and 48 hpi. Upregulation of miR-3976 promoted cell apoptosis and inhibited the parasite burden in HCT-8 cells after C. parvum infection. Luciferase reporter assay indicated that BCL2A1 was a target gene of miR-3976. Co-transfection with miR-3976 and a BCL2A1 overexpression vector revealed that miR-3976 targeted BCL2A1 and suppressed cell apoptosis and promoted the parasite burden in HCT-8 cells. Conclusions The present data indicated that miR-3976 regulated cell apoptosis and parasite burden in HCT-8 cells by targeting BCL2A1 following C. parvum infection. Future study should determine the role of miR-3976 in hosts’ anti-C. parvum immunity in vivo. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection

Sun

Xie

et al. 2023

Parasites Vectors

Self Cite

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“…Several microRNAs were involved in response to C. parvum infection. Cryptosporidium parvum upregulated miR-942-5p expression and downregulated miR-181d expression in HCT-8 cells through TLR2/TLR4-NF-κB signaling [39,40]. Twenty miRNAs, which are involved in cell apoptosis and immune responses, were differentially expressed in human intestinal epithelial cells after C. parvum infection [31].…”

Section: Discussionmentioning

confidence: 99%

Cryptosporidium parvum regulates HCT-8 cell autophagy to facilitate survival via inhibiting miR-26a and promoting miR-30a expression

Jiang

Zhang

et al. 2022

Parasites Vectors

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Background Cryptosporidium parvum is an important zoonotic parasite, which not only causes economic losses in animal husbandry but also harms human health. Due to the lack of effective measures for prevention and treatment, it is important to understand the pathogenesis and survival mechanism of C. parvum. Autophagy is an important mechanism of host cells against parasite infection through key regulatory factors such as microRNAs and MAPK pathways. However, the regulatory effect of C. parvum on autophagy has not been reported. Here, we demonstrated that C. parvum manipulated autophagy through host cellular miR-26a, miR-30a, ERK signaling and P38 signaling for parasite survival. Methods The expression of Beclin1, p62, LC3, ERK and P38 was detected using western blotting in HCT-8 cells infected with C. parvum as well as treated with miR-26a-mimic, miR-30a-mimic, miR-26a-mimic or miR-30a-inhibitor post C. parvum infection. The qPCR was used to detect the expression of miR-26a and miR-30a and the number of C. parvum in HCT-8 cells. Besides, the accumulation of autophagosomes was examined using immunofluorescence. Results The expression of Beclin1 and p62 was increased, whereas LC3 expression was increased initially at 0–8 h but decreased at 12 h and then increased again in C. parvum-infected cells. C. parvum inhibited miR-26a-mimic-induced miR-26a but promoted miR-30a-mimic-induced miR-30a expression. Suppressing miR-30a resulted in increased expression of LC3 and Beclin1. However, upregulation of miR-26a reduced ERK/P38 phosphorylation, and inhibiting ERK/P38 signaling promoted Beclin1 and LC3 while reducing p62 expression. Treatment with miR-26a-mimic, autophagy inducer or ERK/P38 signaling inhibitors reduced but treatment with autophagy inhibitor or miR-30a-mimic increased parasite number. Conclusions The study found that C. parvum could regulate autophagy by inhibiting miR-26a and promoting miR-30a expression to facilitate the proliferation of parasites. These results revealed a new mechanism for the interaction of C. parvum with host cells. Graphical Abstract

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Physiology of Gut Water Balance and Pathomechanics of Diarrhea

Elsasser,

Faulkenberg

2024

Production Diseases in Farm Animals

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Cryptosporidium parvum downregulates miR-181d in HCT-8 cells via the p50-dependent TLRs/NF-κB pathway

Cited by 9 publications

References 33 publications

MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection

MiR-3976 regulates HCT-8 cell apoptosis and parasite burden by targeting BCL2A1 in response to Cryptosporidium parvum infection

Cryptosporidium parvum regulates HCT-8 cell autophagy to facilitate survival via inhibiting miR-26a and promoting miR-30a expression

Physiology of Gut Water Balance and Pathomechanics of Diarrhea

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