Brassinosteroids modulate plant immunity at multiple levels.

U pon detection of microbe-associated molecular patterns (MAMPs), plants usually shift cellular activities from normal growth to defense responses called microbeor pathogen-induced immunity (MTI or PTI) (1, 2). Effective regulation of the tradeoffs between growth and immunity according to physiological and pathological conditions is critical for plant fitness in nature. The leucine-rich repeat receptor kinase (LRR-RK) BAK1 has been considered a candidate for mediating such a tradeoff, because it serves as a coreceptor for ligand-binding LRR-RKs for both steroid hormones and MAMPs, including BRI1, which binds brassinosteroids (BRs), and FLS2, the receptor for bacterial flagellin peptide (flg22) eliciting MTI (3, 4). However, it has remained unclear whether sharing BAK1 provides the benefit of signal cross-talk, or is simply because BAK1 does not determine signaling specificity and thus needs no diversification. Experimental evaluation of BAK1’s role in the interplay between BR and flagellin, as described in two studies in PNAS (5, 6), however, discover complex actions of BR on immune responses, including positive and negative as well as BAK1-dependent and BAK1-independent effects. The steroid hormone BR binds to the extracellular domain of the LRR-RK BRI1 to initiate a phosphorylation cascade leading to BR responsive gene expression, cell elongation, and plant growth (7–9). Ligand-induced BRI1 kinase activation involves association and sequential transphosphorylation with BAK1 (BRI1-associated kinase 1) or its homologs (SERK1, -2, and -4) (10, 11). Activated BRI1 phosphorylates the BSK1 and CDG1 receptor-like cytoplasmic kinases, which activate the BSU1 phosphatase (12); BSU1 dephosphorylates and inactivates the GSK3-like kinase BIN2, which otherwise phosphorylates transcription factors that promote BR-regulated gene expression and plant growth (9) (Fig. 1). BR treatment has been shown to enhance disease resistance in rice and tobacco, but the molecular mechanism has remained unknown (13). Innate immune responses in plants are triggered through recognition of conserved MAMPs at the host cell surface by the pattern-recognition receptors, which are mostly LRR-RKs (2, 14). Well-characterized MAMPs include flagellin (flg22), an 18-aa peptide from the elongation factor Tu (elf18), and chitin from fungal cell wall (2). These MAMPs act through specific pattern-recognition receptors to activate the MAPKs, leading to metabolic changes, such as oxidative burst, that halt microbe proliferation (14). Analogous to BR-induced BRI1 signaling, flg22 binding to FLS2 induces rapid association and transphosphorylation with BAK1 (3), and activated FLS2 phosphorylates the receptor-like cytoplasmic kinase BIK1 to transduce the signal (15, 16) (Fig. 1). Sharing BAK1 as coreceptor, the BRI1 and FLS2 pathways may antagonize each other by competing for BAK1 or enhance each other by increasing the cellular pool of active BAK1 (4). To test whether BR and MAMP signaling modulate each other through BAK1, Albrecht et al. treat wild-type plants with BR and flg22 and analyze the responses at biochemical and physiological levels (6). When applied separately to wild-type plants, BR and flg22 each induced distinct biochemical and gene expression responses, without detectable overlap. When plants were cotreated with BR and flg22, flg22 had no effect on BRinduced responses, but BR significantly decreased flg22-induced MTI responses, including oxidative burst and defense gene expression. The results suggest a unidirectional BR inhibition of PTI responses, whereas flg22 has no effect on BR-induced responses (6). Although consistent with the idea that BRI1–BAK1 complex formation reduces the amount of BAK1 available for FLS2, the observed BR inhibition of flg22 responses surprisingly turned out to be independent of BAK1. Measurement of the FLS2–BAK1 complex using coimmunoprecipitation showed no decrease of BAK1 association with FLS2 by BR treatment. Only a very small fraction of BAK1 was recruited to BRI1, and BR treatment also had little effect on flg22induced phosphorylation of FLS2 or its substrate BIK1. Furthermore, BR treatment also inhibited chitin-induced MTI responses, even though chitin signaling is independent of BAK1, and BR inhibited MTI in the null bak1-4 mutant. These results indicate that, instead of BRI1 recruiting BAK1 away from FLS2, BR inhibits PTI through an unknown signaling step downstream of the cell surface receptors (6). In contrast to the conclusions of Albrecht et al., the report by Belkhadir et al. (5) provides evidence for BR modulation of MTI responses through both BAK1-dependent and independent mechanisms. Both increase and decrease of endogenous BR level compromise flg22induced responses, suggesting that an appropriate endogenous level of BR is required for optimal flg22 signaling. Overexpression of BRI1 greatly reduced the responses induced by MAMPs (flg22, elf18, and peptidoglycans) that require BAK1 for signaling but had little effect on the responses induced by MAMP (chitin) that acts through a BAK1-independent signaling mechanism. These effects of BRI1 overexpression on MAMP responses were cancelled by overexpression of BAK1, and conversely, a cell-death phenotype of plants expressing elevated level of BAK1 was suppressed by overexpression of BRI1. The results demonstrate that BRI1 can recruit BAK1 away from the MAMP receptors (5). Can BRI1-activated BAK1 enhance FLS2 signaling? This was tested using a hyperactive allele of BRI1. Plants expressing BRI1 protein at wild-type levels show an increased level of FLS2 BSU1