Antiviral effect and BMAP28 induction by toll-like receptor 7 after bovine alpha- herpesviruses infection

BURUCÚA M.M; QUINTANA S; COBO E.; POUZO L; ODEÓN A; PÉREZ S; MARIN M.

Simposio; Innate Immunity Mechanisms and Modularion eKeystone symposia; 2021

The cross-talk mechanisms between Toll-like receptors (TLRs) and cathelicidins thatparticipate in airway epithelial host defences remain undefined. TLR7 expression isdifferentially modulated by bovine alpha-herpesvirus (BoHV) 1 and 5 infection. Thiswork investigated cathelicidin expression in the respiratory tract of BoHV-1- and 5-infected calves and whether TLR7 activation modulates cathelicidin expression and viralreplication in bovine respiratory cells in vitro. BMAP28 expression was determined byRT-qPCR from nasal mucosa, tracheal epithelium and lung of infected calves [6 dayspost-infection (pi), n=4] relative to mock-infected animals (n=2). Primary cultures of fetalbovine lung were stimulated with TLR7 agonist (Imiquimod, 5 μg/mL) and infected 1hlater with BoHV-1 or BoHV-5 (MOI: 0.1). Viral titres in supernatants and BMAP28 andTLR7 expression were determined at 6 and 24 hpi and analysed by t-test, MixedProcedure of SAS, and REST software, respectively (P< 0.05). BoHV-5 infectiondecreased BMAP28 mRNA in nasal mucosa and lungs (0.27-fold and 0.07-fold,respectively). In tracheal epithelium of mock-infected calves, BMAP28 expression wasundetectable. However, BoHV infection induced the expression of this cathelicidin. Invitro TLR7 induction after BoHV-1 or BoHV-5 infection was higher in cells stimulatedwith Imiquimod (238-fold and 712-fold, respectively). At 24 hpi, the antiviral effect ofImiquimod was demonstrated by the significant decrease (P< 0.05) observed in viralreplication (105.4 TCID50/mL) with respect to the untreated control (106.6 TCID50/mL).Concomitantly, up-regulation of BMAP28 in BoHV-5 infected-cells was observed (27-fold). Previously, we had found that in nasal mucosa and lung TLR7 expression is onlyinduced by BoHV-1. Interestingly, we observed that this cathelicidin decreases onlyduring BoHV-5 infection. Overall, it is demonstrated that TLR7 activation has aprotective effect and induces BMAP28 expression in bovine respiratory cells, suggestinga relevant interaction for controlling infection. Understanding the modulation of theinnate immune response by TLRs, cathelicidins and their signalling pathways would beuseful for preventive and therapeutic strategies against bovine alpha-herpesvirusesinfections.