Noduler an immune protein augments infection-induced cell proliferation through cross-talking with p38 MAPK

Noduler, an immune protein that mediates nodule formation by binding to specific bacteria and hemocytes was previously reported in the wild tasar silkworm, Antheraea mylitta. However, the molecular mechanism underlying nodulation in lepidopterans remains unclear. The present study is performed to investigate the functional connection between Noduler with various signalling pathways. It was observed that Noduler is an upstream factor in the phenoloxidase cascade and its knockdown has no direct effect on Toll/Imd pathway inducible genes. Additionally, Noduler was shown to stimulate cell proliferation via activation of p38 mitogen-activated protein kinase (MAPK). Inhibition of p38 in the infected hemocytes cultured in vitro resulted in reduced cell proliferation and melanization. These results suggest that Noduler mediates nodulation via p38/MAPK signalling. This is the first report implicating the p38 MAPK signalling pathway in the nodulation response of insects.