Tuberculosis (TB) is a major health problem worldwide. TB infection often results in an extensive inflammatory response that can cause lasting lung damage. Adjunct therapies that can reduce this inflammation without compromising bacterial killing could be of great benefit.Due to a potent ability to regulate their mammalian host’s inflammatory response, the secreted/excreted products of parasitic worms are being explored for the presence of anti-inflammatory modalities with drug-like properties. This study examined the capacity of an immune-modulating peptide secreted by the liver fluke parasite, Fasciola hepatica(FhHDM-1) to modulate mycobacteria induced inflammation.
Primary human macrophages and C57BL6 mice were treated with FhHDM-1 either before or after infection with Mycobacterium tuberculosis H37Rv (M.tb). The effect of FhHDM-1 on the activation of macrophages and host immune response was assessed.
In human macrophages, FhHDM-1 post-treatment inhibited the secretion of pro-inflammatory cytokines, including TNF and IL-6, without reducing macrophage control of intracellular M.tb. In vivo, treatment of M.tb infected mice, with the FhHDM-1 peptide from 14 days post-infection significantly reduced the recruitment of inflammatory monocytes, eosinophils and SiglecFlow alveolar macrophages into the lungs. While treatment with FhHDM-1 did not reduce bacterial specific IFN-g production or control of M.tb growth in the lung, the dissemination of M.tb to the spleen was significantly reduced by day 42.
These data show that FhHDM-1 reduced the inflammatory response induced by M.tb infection, without inhibiting the capacity of primary human macrophages or infected mice to control bacterial growth. Peptide therapy may provide a mechanism to limit the damaging inflammation that is a hallmark of TB infection, without reducing control of infection. Further studies investigating the potential of FhHDM-1 as an adjunct anti-TB therapy are warranted.