Plants lack an adaptive immune system and hence have to rely on their innate immune system for defense against pathogens. The innate immune system that works against bacteria and fungi is divided into two partially overlapping defense systems. PTI is the term for the first system, which consists of pattern recognition receptors, often found on the cell membrane that directly recognize molecular marks of a given pathogen. The prime example is the FLS2 receptor that recognizes a stretch of 22 amino acids highly conserved in the flagellum of bacteria. Activation of PTI often result in a response that changes the cell state to an alerted state. The second system, termed ETI, is based on the direct or indirect recognition of the pathogen. The main proteins responsible for this recognition are the R-proteins, which, in various ways,can recognize either pathogen proteins or endogenous proteins that are altered by the pathogen. Activation of ETI often leads to cell death. Misregulation of R-proteins or endogenous R-protein targets can sometimes result in inappropriate and constitutiveactivation of the ETI response. As a result, mutants in genes of guarded proteins exhibit autoimmune phenotypes. This characteristic can be exploited genetically to decipher the molecular mechanisms behind R-protein activation by, for example, forward genetic screens.The main defense against viruses in plants is the RNA silencing machinery. Indeed, mutants in core small RNA biogenesis factors are hyper-susceptible to viruses, and all known viruses carry proteins dedicated to inhibit RNAi, the so-called silencing suppressors. The core small RNA biogenesis factors are the endonucleases responsible for cleaving dsRNA into small RNA duplexes, namely the DCL1-4 proteins. The infectivity of RNA viruses lacking their silencing suppressor is very low in WT plants,but high in dcl4 dcl2 mutants. This indicates that the main antiviral DCLs are DCL4 and DCL2.An interesting feature of the Arabidopsis thaliana DCLs are the phenotypes observed in the different mutant dcl1-4 combinations. dcl1 dcl4 and the dcl1 dcl3 dcl4 mutants display severe developmental defects as well as anthocyanin accumulation and stunted growth, while any mutant combinations in which, DCL2 is knocked-out are green and relatively big. The phenotype is also seen in single dcl4 mutants albeit at a reduced frequency. Similar phenotypes have been observed in different RNA exosome mutant combinations, and these phenotypes are also DCL2-dependent.In this study, we try to clarify the molecular events leading to DCL2-dependent developmental defects. Chapter I describes our discovery that the DCL2-induced phenotype is correlated with an autoimmune gene expression profile. In this chapter, we also find that the DCL2-dependent phenotype is not ecotype-specific, the phenotype frequency is strongly reduced in hypomorphic dcl4mutants, and cytoplasmic DCL2 activity is likely the cause of the phenotype. We conduct a mutational analysis of DCL2 and find that catalytic activity and an intact helicase domain are required for induction of the phenotype, but that helicase domain mutants retain some antiviral activity.In chapter II we decipher some of the molecular mechanisms behind DCL2-induced autoimmunity. We perform a forward genetic screen in which we isolate several mutants in DCL2 that seemingly retain catalytic endonuclease activity but are unable to induce the autoimmune phenotype. More importantly, we identify two specific R-proteins whose inactivation reduces the frequency of autoimmune plants indicating that these might act downstream of DCL2 in regards to immune activation. These R-proteins are also required for optimal viral resistance in dcl4 mutants but not in WT nor in dcl4 dcl2 double mutants, indicating that they have antiviral properties downstream of DCL2. Finally, we show indications that DCL2 and oneof the R-proteins interact in vivo. These observations inspire us to present a model in which DCL2 has RNAi-independent antiviral properties. The model is deeply inspired by the mammalian viral RNA sensors RIG-I, MDA5 and LGP2. In short, we suggest that DCL2 acts as a viral RNA sensor that activates defense responses via. R-proteins when dsRNA over-accumulates. This model can also explain why we observe an autoimmune phenotype in mutants of RNA processing factors.