Deficiency of innate immunity against P. aeruginosa enhances behavioral avoidance via the HECW-1/NPR-1 module in C. elegans

2021 ◽  
Author(s):  
Hua Bai ◽  
Wei Zou ◽  
Wenhui Zhou ◽  
Keqin Zhang ◽  
Xiaowei Huang

To antagonize infection of pathogenic bacteria in soil and confer increased survival, Caenorhabditis elegans employs innate immunity and behavioral avoidance synchronously as the two main defensive strategies. Although both biological processes and their individual signaling pathways have been partially elucidated, knowledge of their interrelationship remains limited. The current study reveals that deficiency of innate immunity triggered by mutation of the classic immune gene pmk-1 promotes avoidance behavior in C. elegans ; and vice versa. Restoration of pmk-1 expression using the tissue-specific promoters suggested that the functional loss of both intestinal and neuronal pmk-1 is necessary for the enhanced avoidance. Additionally, PMK-1 co-localized with the E3 ubiquitin ligase HECW-1 in OLL neurons and regulated the expressional level of the latter, which consequently affected the production of NPR-1, a G-protein-coupled receptor homologous to the mammalian neuropeptide Y receptor, in RMG neurons in a non-cell-autonomous manner. Collectively, our study illustrates, once the innate immunity is impaired when C. elegans antagonizes bacterial infection, the other defensive strategy of behavioral avoidance can be enhanced accordingly via the HECW-1/NPR-1 module, suggesting that GPCRs in neural circuits may receive the inputs from immune system and integrate those two systems for better adapting to the real-time status.

Planta ◽  
2021 ◽  
Vol 253 (5) ◽  
Author(s):  
Marciel Pereira Mendes ◽  
Richard Hickman ◽  
Marcel C. Van Verk ◽  
Nicole M. Nieuwendijk ◽  
Anja Reinstädler ◽  
...  

Abstract Main conclusion Overexpression of pathogen-induced cysteine-rich transmembrane proteins (PCMs) in Arabidopsis thaliana enhances resistance against biotrophic pathogens and stimulates hypocotyl growth, suggesting a potential role for PCMs in connecting both biological processes. Abstract Plants possess a sophisticated immune system to protect themselves against pathogen attack. The defense hormone salicylic acid (SA) is an important player in the plant immune gene regulatory network. Using RNA-seq time series data of Arabidopsis thaliana leaves treated with SA, we identified a largely uncharacterized SA-responsive gene family of eight members that are all activated in response to various pathogens or their immune elicitors and encode small proteins with cysteine-rich transmembrane domains. Based on their nucleotide similarity and chromosomal position, the designated Pathogen-induced Cysteine-rich transMembrane protein (PCM) genes were subdivided into three subgroups consisting of PCM1-3 (subgroup I), PCM4-6 (subgroup II), and PCM7-8 (subgroup III). Of the PCM genes, only PCM4 (also known as PCC1) has previously been implicated in plant immunity. Transient expression assays in Nicotiana benthamiana indicated that most PCM proteins localize to the plasma membrane. Ectopic overexpression of the PCMs in Arabidopsis thaliana resulted in all eight cases in enhanced resistance against the biotrophic oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Additionally, overexpression of PCM subgroup I genes conferred enhanced resistance to the hemi-biotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000. The PCM-overexpression lines were found to be also affected in the expression of genes related to light signaling and development, and accordingly, PCM-overexpressing seedlings displayed elongated hypocotyl growth. These results point to a function of PCMs in both disease resistance and photomorphogenesis, connecting both biological processes, possibly via effects on membrane structure or activity of interacting proteins at the plasma membrane.


Author(s):  
Martha J. Larsen ◽  
Elizabeth Ruiz Lancheros ◽  
Tracey Williams ◽  
David E. Lowery ◽  
Timothy G. Geary ◽  
...  

Author(s):  
Ramasamy Harikrishnan ◽  
Gunapathy Devi ◽  
Chellam Balasundaram ◽  
Hien Van Doan ◽  
Sanchai Jaturasitha ◽  
...  

2018 ◽  
Vol 6 (4) ◽  
pp. 28 ◽  
Author(s):  
Daniel Matúš ◽  
Simone Prömel

Many vital processes during C. elegans development, especially the establishment and maintenance of cell polarity in embryogenesis, are controlled by complex signaling pathways. G protein-coupled receptors (GPCRs), such as the four Frizzled family Wnt receptors, are linchpins in regulating and orchestrating several of these mechanisms. However, despite being GPCRs, which usually couple to G proteins, these receptors do not seem to activate classical heterotrimeric G protein-mediated signaling cascades. The view on signaling during embryogenesis is further complicated by the fact that heterotrimeric G proteins do play essential roles in cell polarity during embryogenesis, but their activity is modulated in a predominantly GPCR-independent manner via G protein regulators such as GEFs GAPs and GDIs. Further, the triggered downstream effectors are not typical. Only very few GPCR-dependent and G protein-mediated signaling pathways have been unambiguously defined in this context. This unusual and highly intriguing concept of separating GPCR function and G-protein activity, which is not restricted to embryogenesis in C. elegans but can also be found in other organisms, allows for essential and multi-faceted ways of regulating cellular communication and response. Although its relevance cannot be debated, its impact is still poorly discussed, and C. elegans is an ideal model to understand the underlying principles.


2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.


2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.


2020 ◽  
Vol 17 (35) ◽  
pp. 381-390
Author(s):  
Andrei SEVBITOV ◽  
Alla DAVIDYANTS ◽  
Roman BALYKIN ◽  
Anton TIMOSHIN ◽  
Mariya KUZNETSOVA

Periodontal disease in the adult population is one of the most pressing problems of dentistry around the world. Thanks to the introduction of modern technologies in practice, it was possible to identify the main mechanisms of the development of this disease at the molecular and genetic level. The interaction of periodontal pathogens with immune factors of antimicrobial protection of the body is the basis of periodontal tissue inflammation and further leads to the destruction of the alveolar bone. Epithelial cells of the gum mucosa play a crucial role against periodontal pathogenic bacteria. Factors of innate immunity play a role not only in antimicrobial protection, but they also support the conditions necessary for the healing and regeneration of periodontal tissues. Therefore, various therapeutic approaches that affect the factors of innate immunity are considered as effective and promising. Clinical examination and determination of factors of innate immunity were performed in 115 patients. Healthy individuals made up a group of 30 people. Patients with chronic generalized periodontitis with varying degrees of severity were 85 people. Each patient underwent orthopantomography on the orthopantomograph Orthophosis XG DS/Ceph (SIRONA Dental System GmbH, Germany) in order to assess the state of the bone tissue of the jaws (the degree of destruction of the cortical layer, the degree of resorption of the interalveolar partitions). Targeted intraoral radiographs were used to assess the state of bone tissue and the quality of surgical treatment. Immunological methods of research were carried out in several stages. The findings of this article make the claim that the use of autologous complex immunopeptides in the surgical treatment of periodontitis reduces the time of achieving a therapeutic effect 2 times, resulting in the rapid relief of the symptoms of inflammation and acceleration of reparative processes.


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