Immunosuppression and apoptosis activation mediated by p53-Bcl2/Bax signaling pathway -The potential mechanism of goldfish (Carassius auratus Linnaeus) gill disease caused by Myxobolus ampullicapsulatus

Abstract

Myxobolus, a major harmful type of myxospora, is one of the main parasitic pathogens of freshwater fish. Once myxoboliosis occurs, treatment can be extremely difficult. Therefore, clear understandings of the etiology of myxoboliosis and its pathological mechanism are keys for prevention and control. Here, histology, transmission electron microscopy, transcriptome study, tunel assay, and immunohistochemistry were carried out, revealing the morphology, pathological effects as well as host response mechanism of goldfish gill to Myxobolus ampullicapsulatus. Histological studies showed that the mature spores of Myxobolus ampullicapsulatus were composed of three parts, the spore shell, sporoplasm and bottle shaped polar capsule containing double S-shaped polar filaments. Transcriptome analysis revealed that Myxobolus ampullicapsulatus -infected (Myx) goldfish gills were characterized by apoptosis activation mediated by “p53 signaling pathway” with significantly up-regulated apoptosis-related differential genes dominated by p53-Bcl2/Bax signaling pathway. In addition, tunel assay revealed severe gill apoptosis in the Myx group. Transcriptome analysis also revealed that Myx group showed changes in immune response and significantly down-regulated immune-related differential genes. Beyond that, immunohistochemistry showed that there was no significant increase in the number of gill lymphocyte after parasite infection. These results suggest that the pathological mechanism of Myxobolus ampullicapsulatus infection on gills of goldfish may be related to apoptosis and immunosuppression. Subsequent qRT-PCR showed that apoptosis-related genes (Caspase3,Bad, Bax) and anti-inflammatory gene IL-10 were significantly increased, while immune-related pro-inflammatory genes (IL-1β, IL-8) were markedly down-regulated, further verifying the transcriptome results. Based on the above results, we concluded that p53-Bcl2/Bax related networks that dominant the expression of apoptosis genes were activated while immunity was suppressed in the gills of Myxobolus ampullicapsulatus infected goldfish. Our study is not only of benefit to enrich the taxonomy of Myxobolus but also clarifies its pathogenic mechanism, thus providing targets for prevention and control of myxoboliosis.

Transcriptome Analysis of Brain and Skin Reveals Immune Responses to Acute Hypoxia and Reoxygenation in Pseudobagrus ussuriensis

“…Stress signals are transmitted to the p53 protein through post-translational modifications, activating p53 as a transcription factor to initiate processes such as cell cycle arrest, cell senescence, or apoptosis [37]. This enrichment aligned with findings in the transcriptome analysis of goldfish (Carassius auratus Linnaeus) gills infected by Myxobolus ampullicapsulatus, where the role of p53 in triggering apoptosis in fish after infection was illustrated [38]. Furthermore, the FoxO pathway was enriched in both the brain and skin tissues under hypoxia stress.…”

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells

“…In response to DNA and oxidative stress, p53 accumulates into the cytoplasmic matrix, where it interacts with pro-apoptotic proteins, such as Bax and Bak, BH3-only pro-apoptotic protein initiators, and other members Bcl-2 family of proteins. These molecular interactions may directly or indirectly promote MOMP and tumor cell death by apoptosis [ 69 , 70 ].…”

Phospholipase A and acyltransferase 4/retinoic acid receptor responder 3 at the intersection of tumor suppression and pathogen restriction

“…Moreover, as we discussed earlier, PLAAT4 expression during pathogen is under the concerted control of p53, IRF1 and IFNs, which all display pleiotropic effects on diverse cellular pathways other than mTOR signaling. For example, they have been demonstrated to play an important role in inducing apoptosis and/ or pyroptosis (146)(147)(148)(149)(150)(151)(152). While our study has shown that PLAAT4mediated suppression of HAV does not involve cell death (16), it remains to be determined whether mTOR-independent signaling pathways (e.g.…”