Cytokinins for immunity beyond growth, galls and green islands Muhammad Naseem 1 , Mirko Wo ¨ lfling 2 , and Thomas Dandekar 1 1 Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, 97074 Wuerzburg, Germany 2 Division of Tropical Ecology and Animal Biodiversity, University of Vienna, Rennweg 14, 1030 Vienna, Austria Cytokinins are essential plant hormones that control almost every aspect of plant growth and development. Their function in mediating plant susceptibility to fungal biotrophs and gall-causing pathogens is well known. Here we highlight the interaction between cytokinins and salicylic acid pathways. Furthermore, we discuss ways in which cytokinin signaling could crosstalk with plant immune networks. Some of these networks are modulated by pathogens to propagate disease, whereas others help the host to mitigate an infection. The role of cytokinins in plant pathogenesis Cytokinins (CKs) are a highly complex family of N 6 -substi- tuted adenine derivatives and chemically unrelated phe- nylurea-type regulatory molecules. In Arabidopsis (Arabidopsis thaliana), CK perception and signaling are mediated by a two-component system (TCS) involving a canonical phosphorelay mechanism. The binding of CKs to the central CHASE (cyclases/histidine kinases associated sensory extracellular) domain of the HISTIDINE KINASE 2–4 (AHK2–4) receptors initiates a downstream phospho- transfer cascade [1]. This culminates in the phosphoryla- tion of Arabidopsis response regulators (ARRs) through histidine phosphotransfer proteins (AHPs). ARRs are cat- egorized into two types: type-B ARRs function as transcrip- tion factors and positively regulate CK signaling, whereas type-A ARRs negatively regulate CK responses and are transcriptionally regulated by type-B ARRs [1]. The role of CK signaling in governing the dynamics of embryogenesis, the root apical meristem and the shoot apical meristem (SAM), morphogenesis, and the formation of nodules has been studied meticulously [1]. Moreover, CK responses are hijacked by many microbial pathogens to infect their plant hosts [2–4]. Typical examples of CK-mediated pathogene- sis are the establishment of tumor galls (altered morpho- genesis) and the generation of green islands (physiological alterations) (Figure 1). Investigation of these and similar prominent disease phenotypes revealed an overriding message of the involvement of CKs only in mediating plant susceptibility [4–6]. However, CKs have regained attention in recent years because they have also been shown to regulate immune dynamics in plants [7–9]. Here, we highlight the role of CKs in pathogenesis as well as emerging trends in CK signaling and crosstalk with plant immune networks. Furthermore, we discuss per- spectives and future directions in research on CKs in plant immunity. Cytokinins orchestrate microbial pathogenicity mechanisms Owing to their profound effect on the reconfiguration of plant primary as well as secondary metabolism, increased CK concentrations create a new source–sink relationship [4,5]. This culminates in nutrient mobilization, which in turn increases the flow of assimilates, and delays senes- cence. Many plant pathogens redirect these mobilized resources for their own feeding as well as to disrupt the host-mediated defense responses. To invade the host and establish pathogenesis through CKs, microbial pathogens have diverse modi operandi. However, a common strategy is the acquisition of individual genetic repertoires for CK biosynthesis; alternatively, pathogens use the host ma- chinery to cause local increases in CK concentrations [3– 5]. For instance, Agrobacterium tumefaciens efficiently changes the balance between plant auxin and CKs, with concomitant dedifferentiation and the development of crown galls by harboring CK and auxin pathway genes on its Ti (tumor inducing) plasmid (Figure 1). Transforma- tion of Arabidopsis with the nopaline Agrobacterium strain, which contains a mutated Tzs (trans-zeatin synthe- sizing) gene on its Ti-plasmid, results in fewer tumors than infection with a functional Tzs gene strain [3]. Moreover, Arabidopsis CK root treatments also increase tumorigene- sis [3]. Arabidopsis myb family transcription factor 1 (MTF1) impedes Agrobacterium mediated transformation susceptibility. However, A. tumefaciens-secreted CKs are recognized by the AHK3 and AHK4 receptors and decrease the expression of MTF1 through the activation of type-A response regulator ARR3 (Figure 1). It is inferred that A. tumefaciens uses CKs as a tool for altering organogenesis and induces crown galls as well as targeting host resistance factors to mediate its susceptibility. Similarly, the leafy gall pathogen Rhodococcus fascians secrets a combination of various CK species, which are recognized by AHK3 and AHK4 receptors in Arabidopsis and synergistically cause the proliferation of young shoot tissues into differentiated leafy galls [6]. Interestingly, R. fascians challenges its host plant in a ‘trick-with-CK-mix’ fashion, whereby some CK species of bacterial origin that provoke the plant system to continuously proliferate shoot tissue are less vulnerable to host enzymatic degradation. This opens niches for longer bacterial incubations [6]. Besides galls, green islands are metabolically active plant zones on otherwise senescent Forum 1360-1385/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tplants.2014.04.001 Corresponding author: Dandekar, T. (dandekar@biozentrum.uni-wuerzburg.de). TRPLSC-1171; No. of Pages 4 Trends in Plant Science xx (2014) 1–4 1