Vet Microbiol. 2022 Oct;273:109513.doi: 10.1016/j.vetmic.2022.109513. Epub 2022 Jul 15.(IF3.246)

IL-1β induced by PRRSV co-infection inhibited CSFV C-strain proliferation via the TLR4/NF-κB/MAPK pathways and the NLRP3 inflammasome

Dengjin Chen  1 Shengkui Xu  1 Ruijiao Jiang  1 Yating Guo  1 Xintan Yang  1 Yongning Zhang  1 Lei Zhou  1 Xinna Ge  1 Jun Han  1 Xin Guo  2 Hanchun Yang  1

Affiliations

Abstract

PRRSV and CSFV are both the main pathogens of pigs and pose great threats to the pig industry. Previous studies have shown that PRRSV infection or attenuated virus vaccination can reduce the antibody level of attenuated CSFV vaccine and even cause immune failure. The higher pro-inflammatory cytokines induced by PRRSV might play a significant role in inhibiting the proliferation of CSFV-C. However, the molecular mechanism has not been elucidated yet. Here, the effect of IL-1β, a central mediator of immune-regulating inflammatory responses, on CSFV-C proliferation was investigated, as well as the mechanisms responsible for the production of IL-1β in the PRRSV and CSFV-C co-infection systems. The results showed that co-infection could significantly increase IL-1β production both at mRNA and protein levels with the infection progressing, and the IL-1β upregulation was mainly triggered by PRRSV infection. Additional experiments indicated that IL-1β inhibited the proliferation of CSFV-C in a cell-type independent manner at the replication and release stages. Furthermore, the IL-1β production induced via the TLR4/MyD88 pathway and the downstream signaling pathways NF-κB, ERK1/2, P38, and JNK were involved by treatment with specific inhibitors or siRNA knockdown assays. Finally, we clarified that the NLRP3 inflammasome played a meaningful role in the maturation and release of IL-1β. Together, the accumulated results provided a deeper understanding of the vaccination failure of CSFV caused by PRRSV co-infection as well as targets for the development of novel approaches for the vaccination and control of CSF.

Keywords: CSFV; Co-infection; IL-1β; NLRP3 inflammasome; PRRSV; TLR4/NF-κB/MAPKs.

在线客服
在线客服
热线电话
0