Microplitis bicoloratus parasitism promotes cyclophilin D-p53 interaction to induce apoptosis of hemocytes in Spodoptera litura.

Microplitis bicoloratus parasitism can induce apoptosis of hemocytes in the M. bicolortus host, Spodoptera litura. However, it is unclear how M. bicolortus parasitism regulates host signaling pathways to induce apoptosis. Expression of cyclophilin D (CypD) and p53 was significantly upregulated in S. litura hemocytes at 6 days postparasitization. In the parasitized hemocytes, there was mitochondrial membrane potential (△Ψm ) loss, cytochrome c (Cyt C) release from mitochondria, and caspase-3 activation. These occurred while hemocytes were undergoing upregulation of CypD and p53. Parasitism also promoted the interaction between CypD and p53. CypD silencing could rescue the apoptotic phenotypes induced by parasitism, but had no effect on apoptosis in unparasitized S. litura. These findings suggest that the CypD-p53 pathway may be an important component of the parasitism-induced immunosuppressive response and establish a basis for further studies of parasitoid/host interactions.

Microplitis bicoloratus bracovirus regulates cyclophilin A-apoptosis-inducing factor interaction to induce cell apoptosis in the insect immunosuppressive process.

Microplitis bicoloratus bracovirus (MbBV) induces apoptosis in hemocytes of the host (Spodoptera litura) via the cyclophilin A (CypA)-mediated signaling pathway. However, the mechanisms underlying CypA-mediated signaling during apoptosis remain largely unknown. Therefore, in this study, we investigated how CypA and apoptosis-inducing factor (AIF) interact during MbBV-mediated apoptosis. Our findings showed that MbBV induces apoptosis through the CypA-AIF axis of insect immune suppression. In MbBV-infected Spli221 cells, both the expression of the cypa gene and the release of AIF from the mitochondria increased the number of apoptotic cells. CypA and AIF underwent concurrent cytoplasm-nuclear translocation. Conversely, blocking of AIF release from mitochondria not only inhibited the CypA-AIF interaction but also inhibited the cytoplasmic-nuclear translocation of AIF and CypA. Importantly, the survival of the apoptotic phenotype was significantly rescued in MbBV-infected Spli221 cells. In addition, we found that the cyclosporine A-mediated inhibition of CypA did not prevent the formation of the CypA and AIF complex; rather, this only suppressed genomic DNA fragmentation. In vitro experiments revealed direct molecular interactions between recombinant CypA and AIF. Taken together, our results demonstrate that the CypA-AIF interaction plays an important role in MbBV-induced innate immune suppression. This study will help to clarify aspects of insect immunological mechanisms and will be relevant to biological pest control.