The sugar-beet cyst nematode effector Hs2B11 targets the Arabidopsis serine protease inhibitor AtPR-6 to favor parasitism

Cyst nematodes secrete effector proteins to manipulate host cell biology and suppress immunity, yet the mechanisms underlying these interactions remain largely unexplored. In this study, we characterize the function of Hs2B11, a Heterodera schachtii effector that was previously shown to be expressed in the dorsal gland of sugar-beet cyst nematodes (BCN). Here, we report that in Arabidopsis thaliana Hs2B11 functions as an immune regulator that modulates the production of elicitor-induced oxidative species, likely to favor parasitism. To elucidate the molecular basis of this immune suppression, we performed a yeast-two-hybrid screen and identified the host serine protease inhibitor AtPR-6 as a direct interactor of Hs2B11. We show that AtPR-6 acts as a positive regulator of plant immunity; its expression is induced upon nematode infection and knock-out of AtPR-6 compromises oxidative species production leading to higher susceptibility to H. schachtii infection. Conversely, AtPR-6 overexpression enhances immune responses resulting in increased resistance to BCN infection. Detailed analysis of this interaction demonstrated that Hs2B11 interacts with AtPR-6 using its carboxyl-terminal domain. AlphaFold2 predicts that the C-terminal domain forms a beta-solenoid-like structure with a ladder of serine residues organized across one of its surfaces. We propose that using this interface, Hs2B11 targets AtPR-6 via molecular titration, preventing the inhibitor from regulating host proteases that control immune signaling. These findings highlight a counter-defense strategy where a nematode effector neutralizes a specific host protease inhibitor to subvert plant immunity.