bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.04.06.438581

The molecular interplay of the establishment of an infection - gene expression of Diaphorina citri gut and Candidatus Liberibacter asiaticus

Abstract

Candidatus Liberibacter asiaticus (CLas) is one the causative agents of greening disease in citrus, an unccurable, devastating disease of citrus worldwide. CLas is vectored by Diaphorina citri, and the understanding of the molecular interplay between vector and pathogen will provide additional basis for the development and implementation of successful management strategies. We focused in the molecular interplay occurring in the gut of the vector, a major barrier for CLas invasion and colonization. We investigated the differential expression of vector and CLas genes by analyzing a de novo reference metatranscriptome of the gut of adult psyllids fed of CLas-infected and healthy citrus plants for 1-2, 3-4 and 5-6 days. CLas regulates the immune response of the vector affecting the production of reactive species of oxygen and nitrogen, and the production of antimicrobial peptides. Moreover, CLas overexpressed peroxiredoxin in a protective manner. The major transcript involved in immune expression was related to melanization, a CLIP-domain serine protease we believe participates in the wounding of epithelial cells damaged during infection, which is supported by the down-regulation of pangolin. We also detected that CLas modulates the gut peristalsis of psyllids through the down-regulation of titin, reducing the elimination of CLas with faeces. The up-regulation of the neuromodulator arylalkylamine N-acetyltransferase implies CLas also interferes with the double brain-gut communication circuitry of the vector. CLas colonizes the gut by expressing two Type IVb pilin flp genes and several chaperones that can also function as adhesins. We hypothesized biofil formation occurs by the expression of the cold shock protein of CLas. We also describe the interplay during cell invasion and modification, and propose mechanisms CLas uses to invade the host hemocel. We identified several specific targets for the development of strategies directed to interfere with the successful utilization of the psyllid vector by this pathogen. Author SummaryHuanglongbing (HLB) or greening is an incurable disease causing severe damage to citrus production, making citrus industrial activity unsustainable in several countries around the world. HLB is caused by three species of Candidatus Liberibacter. Ca. L. asiaticus (CLas), vectored by the psyllid Diaphorina citri, is the prevalent species. Attempts to apply new technologies in the development of strategies for disease and pest management are been made. However, we still miss basic information on this system to efficiently apply the current technologies and envisage the implementation of new approaches for pest control, despite the relevant scientific contribution available. One major gap is regarded to the molecular interplay between CLas and its vector. We focused our attention in the molecular interplay occurring at the first relevant interaction of CLas and D. citri, represented by the gut barrier. We report the transcriptional activity of CLas during the invasion and establishment of the infection in the gut of the vector, as well as the transcriptional activity of the vector in response to the infection. We identified several host genes that are targeted and regulated by CLas as well as several CLas genes that are promising targets for the application of new management strategies.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bento, F. d. M. M., Darolt, J. C., Merlin, B. L., Pena, L., Wulff, N. A., Consoli, F. L.. 2021-04-06. The molecular interplay of the establishment of an infection - gene expression of Diaphorina citri gut and Candidatus Liberibacter asiaticus. https://doi.org/10.1101/2021.04.06.438581

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

SilencioM: silencing connected interfering oligonucleotides against MAPT as a potential disease modifying therapeutic for tauopathies

Tauopathies are a diverse group of neurodegenerative diseases whose pathogenesis involves brain accumulation of misfolded, pathological tau (Microtubule Associated Protein Tau, MAPT). More than twenty tauopathies have been identified thus far that collectively impact millions of people worldwide, of which the most common is Alzheimer's disease (AD). Despite substantial efforts to develop drugs for tauopathies, no effective treatments currently exist, highlighting the urgent need for therapeutics to combat these prevalent and ruinous neurodegenerative diseases. Strategies that target tau are likely to have the greatest impact since tau is the proximal cause of their pathogenesis. Small interfering RNAs (siRNAs) have emerged as a powerful class of precision therapeutics that silence disease-causing genes through RNA interference with favorable safety profiles. Delivery challenges are rapidly being addressed, and siRNA-based approaches are poised to transform the therapeutic landscape of neurological diseases. In this study, we describe SilencioM (Silencing connected interfering oligonucleotides against MAPT) and show its efficacy in markedly reducing tau pathology after a single intracerebroventricular injection in PS19 mice, a mouse model of severe tauopathy. SilencioM targets human, primate, rat and mouse ortholog genes; thus, the same compound can proceed from efficacy studies to Investigational New Drug Application (IND)-enabling studies. SilencioM is simple to manufacture and is administered without encapsulation in lipid nanoparticles and without requirements for lipophilic conjugation, making it a promising candidate for further development as a novel therapeutic for tauopathies, including AD.

pathology↗

Relative expression of THY1 and PDGFRA in equine endometrosis in relation to severity, histopathological features and endometrial transcripts

Equine endometrosis is a degenerative uterine disease characterized by periglandular fibrosis and represents a major cause of subfertility in mares. While stromal cell activation results in pathological tissue remodeling, the involvement of cell-surface integrators (THY1) and growth factor receptors (PDGFRA) was not researched. This study evaluated the relative mRNA expression of THY1 and PDGFRA across Kenney and Doig (KD) endometrosis categories and specific histopathological features. Additionally, transcriptomic correlation profiles between target genes and markers of myofibroblast differentiation (ACTA2), cellular proliferation (MKI67), and steroid hormone receptors (ESR1, PGR) were analyzed. Endometrial samples (n = 47) were quantified using RT-qPCR. Relative mRNA expression of THY1 differed significantly across KD categories (p = 0.014), exhibiting a transient upregulation in category IIA compared with category I (p = 0.009) and category IIB (p = 0.002). Furthermore, THY1 relative mRNA expression was significantly elevated in tissues with glandular basal lamina disruption (p = 0.022). Conversely, PDGFRA relative mRNA expression remained stable across disease categories (p > 0.05). THY1 relative mRNA expression correlated very strongly with ACTA2 ({rho} = 0.875, p < 0.001) and strongly with ESR1 ({rho} = 0.652, p < 0.001). PDGFRA relative mRNA expression exhibited a very strong positive correlation with ESR1 ({rho} = 0.864, p < 0.001) and a strong positive correlation with MKI67 ({rho} = 0.674, p < 0.001). These results indicate that THY1 transcription is transiently induced during early stromal remodeling and basal lamina loss, whereas PDGFRA maintains constitutive transcript stability. Observed co-expression profiles reflect statistical co-variation among stromal remodeling, proliferative, and steroid-responsive cell populations in bulk tissue.

pathology↗

CD8+ T-cells protect against experimental atherosclerosis through antigen specific interactions in the plaque

Atherosclerosis is a chronic inflammatory disease with a significant adaptive immune component. CD8+ T cells accumulate in plaques and display signatures of antigen-specific activation. However, whether this accumulation is driven by local antigen recognition and what functional consequences follow, remains poorly understood. Here we address this gap of knowledge using loss- and gain-of-function experiments. Atherosclerotic Rag-/-Ldlr-/- mice received adoptively transferred wildtype or antigen-restricted CD8+ T cells alongside CD4+ T cells to distinguish antigen-specific from antigen-independent responses. In a complementary model, ApobOVA-TGxLdlr-/- mice, expressing an ovalbumin-tagged variant of the atherosclerosis-associated ApoB100 protein, enabled OT-I CD8+ T cells to function as atherosclerosis-antigen-specific CD8+ T cells. T-cell distribution, activation and phenotype were assessed systemically and within lesions, plaque burden and composition were quantified histologically. Wildtype CD8+ T cells accumulated significantly more in aortic lesions compared to antigen-restricted CD8+ T cells, and exhibited increased activation, exhaustion and cytokine secretion, indicating that plaque-infiltrating T cells are predominantly antigen-specific. Perturbing antigen-specific CD8+ T-cell interactions significantly decreased plaque stability index, suggesting a protective role for antigen-specific CD8+ T cells. In ApobOVA-TGxLdlr-/- mice, OT-I T cells accumulated at high frequency in the liver, consistent with hepatic ApoB100-expression, and were found in circulation and aorta. Histological analysis revealed reduced plaque burden in OT-I recipients, reproducing an atheroprotective effect of antigen-specific CD8+ T-cell responses. Plaque reduction coincided with reduced TUNEL, but similar Caspase 3 staining, suggesting OT-I transfer results in reduced secondary necrosis. In line with this, CD47 expression in OT-I recipient mice was reduced and in vitro, OT-I but not antigen non-specific CD8+ T cells reduced expression of CD47 on OVA-presenting foam cells. CD8+ T-cell accumulation in experimental atherosclerosis is driven primarily by antigen-specific interactions and such responses are associated with plaque stabilization and reduced lesion formation, potentially through induction of apoptosis and prevention of secondary necrosis

pathology↗