Immunoregulatory and antiviral effect mediated by TLR7 and BMAP28 interaction in bovine alphaherpesvirus-infected respiratory primary cultures

Abstract

Varicellovirus bovinealpha 1 and 5 (formerly bovine alphaherpesvirus type 1 and 5, BoAHV-1 and BoAHV-5) are closely related and can be isolated from similar clinical conditions, including respiratory and nervous diseases, genital infections and abortion. Pathogens´ activation of toll-like receptors (TLRs) induces the expression of proinflammatory cytokines and antimicrobial peptides such as cathelicidins. Cathelicidins are presumed to act as endogenous ligands of TLRs, stimulating, in turn, their activation. Cattle´s innate immune responses mediated by TLRs and cathelicidins remain undefined. This work aimed to study the interaction mechanisms between TLR7 and a bovine cathelicidin (bovine myeloid antimicrobial peptide (BMAP)28 and their influence on the replication of BoAHV-1 and BoAHV-5. It was shown that in vitro infection by BoAHV-1 and BoAHV-5 induces the innate immune responses associated with TLR7 and BMAP28 in primary cultured bovine fetal lung cells. Pretreatment with TLR7 agonist (imiquimod) or an endogenous cathelicidin inductor (sodium butyrate) enhanced the innate immune response to BoAHV mediated by TLR7 signalling, BMAP28, TNFα, IFNβ and IFNγ. It exerted an antiviral effect, decreasing BoAHV replication. Inhibition of endosomal TLRs and downstream signalling molecules MAPK, NF-κβ, IKK-2, and JNK II counteracted these antiviral effects. Therefore, BMAP28 shows novel roles in modulating the immune response induced by TLR7 activation through signalling pathways involving kinases and NF-κβ. Enhancing TLR7 and endogenous cathelicidin expression could be a complementary tool for the prevention and/or control of BoAHV infections.