Here, we explore the potential role of
formyl peptide receptor 2 (FPR2) during Brucella abortus
infection. FPR2 manipulation affected B. abortus internalization but not its growth within macrophages. During the activation of FPR2 induced by its agonist AGP-8694, a high level of Brucella uptake was accompanied by an increase in ERK phosphorylation, while intracellular survival at 24 h postincubation was observed to be associated with slightly reduced
nitrite accumulation but augmented
superoxide anion production. Attenuated secretion of
IL-6 and
IL-10 were observed 48 h postincubation in the bone marrow-derived macrophages (BMDMs) treated with the FPR2 antagonist WRW4. An opposite pattern of bacterial uptake was observed upon treatment with the FPR2 antagonist, but no significant changes in the activation of MAPKs or the production of
nitrite or
superoxide anion were observed. Interestingly, AGP-8694 treatment of mice did not lead to differences in spleen or liver weight but slightly enhanced bacterial proliferation was observed in the spleen. Although the weights of the spleen or liver did not differ, WRW4 treatment led to reduced bacterial proliferation in the spleen. Furthermore, FPR2 antagonist treatment was associated with high serum levels of the proinflammatory
cytokines IL-12, TNF-α, IFN-γ and MCP-1, while the production of TNF-α was inhibited in AGP-8694-treated mice.
IL-6 and
IL-10 levels were slightly increased in AGP-8694-treated mice at 24 h postinfection. Our findings demonstrated the contribution of FPR2 via manipulating this receptor using its reported agonist AGP-8694 and antagonist WRW4 in both in vitro and in vivo systems. Although activation of the receptor did not consistently induced
Brucella infection, FPR2 inhibition may be a promising strategy to treat
brucellosis in animals which encourages further investigation.