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Larson, E. A.

Publications and source records attributed to Larson, E. A..

2 recordsLinked to original sources

Biosynthesis of a major plant immunity hormone, salicylate, changed drastically during evolution of flowering plants

Salicylate (SA) is a major plant immunity hormone that activates immune responses against biotrophic pathogens. Between two known SA biosynthetic routes, the isochorismate synthase (ICS) and phenylalanine ammonia-lyase (PAL) pathways, which predominates in particular flowering plants has remained uncertain. We established a straightforward approach that directly quantifies the relative contributions of the ICS and PAL pathways and can also reveal an alternative, non-ICS/PAL route. In this approach, SA and shikimate (ShA), the precursor of SA in the ICS and PAL pathways, were metabolically labeled with [13C6]glucose in leaf tissue. We analyzed the LC-MS/MS data of the compounds using a metabolism-guided statistical model (the ICS-PAL model). This analysis allowed tracking of the origins of their ring and carboxyl carbons and, consequently, determination of the main SA biosynthetic routes. We surveyed SA biosynthetic routes in plants of the order Brassicales, other diverse eudicots, a monocot, magnoliids, and basal angiosperms. We found that the main SA biosynthetic routes changed at least twice during evolution of flowering plants: from a non-ICS/PAL pathway to the PAL pathway around the divergence time of monocots, and from the PAL pathway to the ICS pathway within Brassicales. Application of another metabolism-guided statistical model (the PKS-PAL model) to the SA data suggested that the non-ICS/PAL pathway involves a type III polyketide synthase (PKS). Typically, once a biosynthetic pathway is established for an important molecule, it is conserved in the subsequent lineage. SA biosynthesis in flowering plants took an unusual evolutionary path in which the pathways changed drastically multiple times. This unconventional evolutionary mechanism was employed for a major immunity hormone, likely due to rapid evolution of biotic environments, such as pathogens and insects that attack plants.

plant biology↗

IFNγ regulates MR1 transcription and antigen presentation

Antigen presentation molecules play key roles in activating T cell immunity. Multiple complementary pathways are known to regulate classical MHC-I molecules at transcriptional, translational, and post-translational levels. Intracellular trafficking mechanisms dictating post-transcriptional regulation of MR1, the MHC Class I-like molecule which restricts MAIT cells, have been an area of focus; however, little is known about MR1 transcriptional regulation. We demonstrate that, similar to classical MHC-I, interferons regulate MR1 transcription. Treatment of airway epithelial cells (AEC) with recombinant IFN{beta} or IFN{gamma} variably increased MR1 transcripts, while only IFN{gamma} significantly increased surface MR1 expression and enhanced antigen presentation to MAIT cells. The MR1 promoter contains binding motifs for interferon regulatory factor 1 (IRF1), an important MHC-I transcription factor. IRF1 knockout reduced IFN{gamma}-stimulated MR1 transcription, surface expression, and antigen presentation. Conversely, knockout of Nod-like Receptor family CARD domain containing 5 (NLRC5), a critical component of IFN{gamma}-induced MHC-I transcription, did not significantly impact MR1 expression. These findings were corroborated in primary human AEC treated with IFN{gamma}. In co-culture experiments, MAIT cells incubated with Streptococcus pneumoniae-infected primary AEC produced sufficient IFN{gamma} to stimulate upregulation of MR1 expression. Our data support a model where IFN{gamma} from activated MAIT cells or another source stimulates IRF1-dependent MR1 expression and antigen presentation, leading to greater MAIT cell activation. A robust MR1-dependent MAIT cell response may be beneficial for early infection responses, allowing minimal antigen stimulus to generate greater proinflammatory activity.

immunology↗