Impact of surface receptors TLR2, CR3, and FcRIII on Rhodococcus equi phagocytosis and intracellular survival in macrophages. Academic Article uri icon

abstract

  • The virulence-associated protein A (VapA) produced by virulent Rhodococcus equi allows it to replicate in macrophages and cause pneumonia in foals. It is unknown how VapA interacts with mammalian cell receptors, but intracellular replication of avirulent R. equi lacking vapA can be restored by supplementation with recombinant VapA (rVapA). Our objectives were to determine whether the absence of the surface receptors Toll-like receptor 2 (TLR2), complement receptor 3 (CR3), or Fc gamma receptor III (FcRIII) impacts R. equi phagocytosis and intracellular replication in macrophages, and whether rVapA restoration of virulence in R. equi is dependent upon these receptors. Wild-type (WT) murine macrophages with TLR2, CR3, or FcRIII blocked or knocked out (KO) were infected with virulent or avirulent R. equi, with or without rVapA supplementation. Quantitative bacterial culture and immunofluorescence imaging were performed. Phagocytosis of R. equi was not affected by blockade or KO of TLR2 or CR3. Intracellular replication of virulent R. equi was not affected by TLR2, CR3, or FcRIII blockade or KO; however, avirulent R. equi replicated in TLR2-/- and CR3-/- macrophages but not in WT and FcRIII-/-. rVapA supplementation did not affect avirulent R. equi phagocytosis but promoted intracellular replication in WT and all KO cells. By demonstrating that TLR2 and CR3 limit replication of avirulent but not virulent R. equi and that VapA-mediated virulence is independent of TLR2, CR3, or FcRIII, our study provides novel insights into the role of these specific surface receptors in determining the entry and intracellular fate of R. equi.

published proceedings

  • Infect Immun

author list (cited authors)

  • da Silveira, B. P., Barhoumi, R., Bray, J. M., Cole-Pfeiffer, H. M., Mabry, C. J., Burghardt, R. C., Cohen, N. D., & Bordin, A. I.

complete list of authors

  • da Silveira, Bibiana Petri||Barhoumi, Rola||Bray, Jocelyne M||Cole-Pfeiffer, Hannah M||Mabry, Cory J||Burghardt, Robert C||Cohen, Noah D||Bordin, Angela I

editor list (cited editors)

  • Kline, K. A.

publication date

  • November 2023