Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Salicylic Acid: Biosynthesis and Signaling.

Salicylic acid (SA) is an essential plant defense hormone that promotes immunity against biotrophic and semibiotrophic pathogens. It plays crucial roles in basal defense and the amplification of local immune responses, as well as the establishment of systemic acquired resistance. During the past three decades, immense progress has been made in understanding the biosynthesis, homeostasis, perception, and functions of SA. This review summarizes the current knowledge regarding SA in plant immunity and other biological processes. We highlight recent breakthroughs that substantially advanced our understanding of how SA is biosynthesized from isochorismate, how it is perceived, and how SA receptors regulate different aspects of plant immunity. Some key questions in SA biosynthesis and signaling, such as how SA is produced via another intermediate, benzoic acid, and how SA affects the activities of its receptors in the transcriptional regulation of defense genes, remain to be addressed.

Brassinosteroids Antagonize Jasmonate-Activated Plant Defense Responses through BRI1-EMS-SUPPRESSOR1 (BES1).

Brassinosteroids (BRs) and jasmonates (JAs) regulate plant growth, development, and defense responses, but how these phytohormones mediate the growth-defense tradeoff is unclear. Here, we identified the Arabidopsis (Arabidopsis thaliana) dwarf at early stages1 (dwe1) mutant, which exhibits enhanced expression of defensin genes PLANT DEFENSIN1.2a (PDF1.2a) and PDF1.2b The dwe1 mutant showed increased resistance to herbivory by beet armyworms (Spodoptera exigua) and infection by botrytis (Botrytis cinerea). DWE1 encodes ROTUNDIFOLIA3, a cytochrome P450 protein essential for BR biosynthesis. The JA-inducible transcription of PDF1.2a and PDF1.2b was significantly reduced in the BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1) gain-of-function mutant bes1- D, which was highly susceptible to S. exigua and B. cinerea BES1 directly targeted the terminator regions of PDF1.2a/PDF1.2b and suppressed their expression. PDF1.2a overexpression diminished the enhanced susceptibility of bes1- D to B. cinerea but did not improve resistance of bes1- D to S. exigua In response to S. exigua herbivory, BES1 inhibited biosynthesis of the JA-induced insect defense-related metabolite indolic glucosinolate by interacting with transcription factors MYB DOMAIN PROTEIN34 (MYB34), MYB51, and MYB122 and suppressing expression of genes encoding CYTOCHROME P450 FAMILY79 SUBFAMILY B POLYPEPTIDE3 (CYP79B3) and UDP-GLUCOSYL TRANSFERASE 74B1 (UGT74B1). Thus, BR contributes to the growth-defense tradeoff by suppressing expression of defensin and glucosinolate biosynthesis genes.

Arabidopsis thaliana Plants Engineered To Produce Astaxanthin Show Enhanced Oxidative Stress Tolerance and Bacterial Pathogen Resistance.

Carotenoids play key roles in photosynthesis and photoprotection. Few multicellular plants produce the ketocarotenoid astaxanthin, a strong antioxidant; however, Arabidopsis thaliana lines overexpressing the Chlamydomonas reinhardtii ß-carotene ketolase (CrBKT) accumulated high amounts of astaxanthin in the leaves. In this study, we investigated the changed regulation of key metabolic pathways and the tolerance of the engineered plants to biotic and abiotic stresses resulting from the heterologous expression of CrBKT. Transcriptome analysis identified 1633 and 1722 genes that were differentially expressed in the leaves and siliques, respectively, of CrBKT-overexpressing plants (line CR5) as compared to wild-type Arabidopsis. These genes were enriched in the carotenoid biosynthetic pathways, and plant hormone biosynthesis and signaling pathways. In particular, metabolic profiling showed that, as compared to the wild-type leaves and siliques, overexpression of CrBKT increased the levels of most amino acids, but decreased the contents of sugars and carbohydrates. Furthermore, CR5 plants had lower sensitivity to abscisic acid (ABA) and increased tolerance to oxidative stress. CR5 plants also exhibited enhanced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Our study provides insight into the regulation of carotenoids and the related pathways, which may be involved in plant response to oxidative stress and pathogen infection.

Opposite Roles of Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Transcriptional Regulation of Plant Immunity.

Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis NPR1 and NPR3/NPR4 were previously shown to bind SA and all three proteins were proposed as SA receptors. NPR1 functions as a transcriptional co-activator, whereas NPR3/NPR4 were suggested to function as E3 ligases that promote NPR1 degradation. Here we report that NPR3/NPR4 function as transcriptional co-repressors and SA inhibits their activities to promote the expression of downstream immune regulators. npr4-4D, a gain-of-function npr4 allele that renders NPR4 unable to bind SA, constitutively represses SA-induced immune responses. In contrast, the equivalent mutation in NPR1 abolishes its ability to bind SA and promote SA-induced defense gene expression. Further analysis revealed that NPR3/NPR4 and NPR1 function independently to regulate SA-induced immune responses. Our study indicates that both NPR1 and NPR3/NPR4 are bona fide SA receptors, but play opposite roles in transcriptional regulation of SA-induced defense gene expression.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Perception of Salicylic Acid in Physcomitrella patens.

Salicylic acid (SA) is a key signaling molecule in plant immunity. Two types of SA receptors, NPR1 and NPR3/NPR4, were reported to be involved in the perception of SA in Arabidopsis. SA is also synthesized in the non-vascular moss Physcomitrella patens following pathogen infection. Sequence analysis revealed that there is only one NPR1/NPR3/NPR4-like protein in P. patens. This agrees with the phylogenetic study that showed the divergence of NPR1 and NPR3/NPR4 from the same ancestor during the evolution of higher plants. Intriguingly, expression of the P. patens NPR1/NPR3/NPR4-like gene in Arabidopsis does not complement the constitutive defense phenotype of the npr3 npr4 double mutant, but can partially rescue the mutant phenotypes of npr1-1, suggesting that it functions as an NPR1-like positive regulator of SA-mediated immunity and P. patens does not have an SA receptor functioning similarly as NPR3/NPR4. Future characterization of the P. patens NPR1-like protein and analysis of its functions through knockout and biochemical approaches will help us better understand how SA is perceived and what its functions are in P. patens.