Title : Targeting Toll Like Receptor 2: porcine macrophages primed for enhanced cytokine responses and increased susceptibility to African swine fever infection
Abstract:
Toll-like receptor 2 (TLR2) ligands are attracting significant attention as prophylactic and immunopotentiator agents against several viruses. We investigated the impact of a synthetic diacylated lipopeptide (Mag-Pam2Cys_P48) on porcine monocyte-derived macrophages (moM?) and we observed that it induced up-regulation of activation markers and release of pro-inflammatory cytokines. Then, we investigated its role in modulating macrophages responses against African swine fever virus (ASFV), the aetiological agent of a great threat to the global pig industry. The impact of Mag-Pam2Cys_P48 on moM? responses to two ASFV isolates of diverse virulence (the attenuated NH/P68 and the virulent 26544/OG10) was analyzed. Untreated and Mag-Pam2Cys_P48-treated moM? were infected using a multiplicity of infection (MOI) of 1, and we observed that Mag-Pam2Cys_P48 did not influence virus infection nor its modulation of surface markers expression 21 h post-infection. However, Mag-Pam2Cys_P48 treated moM? released higher levels of IL-1α, IL-1β, IL-1Ra, IL-18 in response to infection with the attenuated NH/P68 ASFV compared to mock-infected controls. The effect of this diacylated lipopeptide to influence ASFV ability to grow in moM? was also investigated. When infected using a MOI of 0.01, Mag-Pam2Cys_P48 enhanced the ability of both NH/P68 and 26544/OG10 strains to replicate in moM?. Although our data suggest caution in the use of TLR2 agonists as prophylactic or immunopotentiator agents against ASFV, we provided a better understating of how the virus eludes host defenses, hopefully aiding the rational design of therapeutic strategies against ASFV.
What will audience learn from your presentation?
- Immunomodulatory impact of a TLR2 agonist on porcine macrophages
- Impact of a TLR2 agonist on porcine macrophages infection and responses to ASFV, one of the greatest threats to the swine industry
- Better understanding on how ASFV evades host defenses
Differences in macrophage responses to ASFV strains of diverse virulence