Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans' Response to Prenol, an Odor Associated with Nematode-Infected Insects

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C. elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology

First report of Tarantula-parasitic nematode Tarantobelus jeffdanielsi from Los Angeles, California.

Tarantobelus jeffdanielsi is a recently described nematode parasite of tarantulas, originally isolated from a tarantula breeder in Virginia Beach, VA. We describe a new case of this parasite infecting tarantulas at a breeding facility in Los Angeles, California. Nematodes were isolated from the oral cavity of a captive bred Psalmophoeus iriminia commonly referred to as a Venezuelan sun tiger tarantula. rDNA sequencing was conducted to identify the species and generate a phylogeny tree

Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA)

The role of pulmonary free fatty acid receptor 4 (FFAR4) is not fully elucidated and we aimed to clarify the impact of FFAR4 on the pulmonary immune response and return to homeostasis. We employed a known high-risk human pulmonary immunogenic exposure to extracts of dust from swine confinement facilities (DE). WT and Ffar4-null mice were repetitively exposed to DE via intranasal instillation and supplemented with docosahexaenoic acid (DHA) by oral gavage. We sought to understand if previous findings of DHA-mediated attenuation of the DE-induced inflammatory response are FFAR4-dependent. We identified that DHA mediates anti-inflammatory effects independent of FFAR4 expression, and that DE-exposed mice lacking FFAR4 had reduced immune cells in the airways, epithelial dysplasia, and impaired pulmonary barrier integrity. Analysis of transcripts using an immunology gene expression panel revealed a role for FFAR4 in lungs related to innate immune initiation of inflammation, cytoprotection, and immune cell migration. Ultimately, the presence of FFAR4 in the lung may regulate cell survival and repair following immune injury, suggestive of potential therapeutic directions for pulmonary disease

Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA)

The role of pulmonary free fatty acid receptor 4 (FFAR4) is not fully elucidated and we aimed to clarify the impact of FFAR4 on the pulmonary immune response and return to homeostasis. We employed a known high-risk human pulmonary immunogenic exposure to extracts of dust from swine confinement facilities (DE). WT and Ffar4-null mice were repetitively exposed to DE via intranasal instillation and supplemented with docosahexaenoic acid (DHA) by oral gavage. We sought to understand if previous findings of DHA-mediated attenuation of the DE-induced inflammatory response are FFAR4-dependent. We identified that DHA mediates anti-inflammatory effects independent of FFAR4 expression, and that DE-exposed mice lacking FFAR4 had reduced immune cells in the airways, epithelial dysplasia, and impaired pulmonary barrier integrity. Analysis of transcripts using an immunology gene expression panel revealed a role for FFAR4 in lungs related to innate immune initiation of inflammation, cytoprotection, and immune cell migration. Ultimately, the presence of FFAR4 in the lung may regulate cell survival and repair following immune injury, suggestive of potential therapeutic directions for pulmonary disease

Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans' Response to Prenol, an Odor Associated with Nematode-Infected Insects.

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C . elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology

Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans' Response to Prenol, an Odor Associated with Nematode-Infected Insects.

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. elegans respond to prenol (3-methyl-2-buten-1-ol), an odor associated with EPN infections. However, it is unclear how C. elegans responds to prenol. By utilizing natural variation and genetic neuron ablation to investigate the response of C . elegans to prenol, we found that the AWC neurons are involved in the detection of prenol and that several genes (including dcap-1, dcap-2, and clec-39) influence response to this odorant. Furthermore, we identified that the response to prenol is mediated by the canonically proposed pathway required for other AWC-sensed attractants. However, upon testing genetically diverse isolates, we found that the response of some strains to prenol differed from their response to isoamyl alcohol, suggesting that the pathways mediating response to these two odorants may be genetically distinct. Further, evaluations leveraging natural variation and genome wide association revealed specific genes that influence nematode behavior and provide a foundation for future studies to better understand the role of prenol in nematode behavioral ecology

Parasitic nematode secreted phospholipase A2 suppresses cellular and humoral immunity by targeting hemocytes in Drosophila melanogaster

A key aspect of parasitic nematode infection is the nematodes' ability to evade and/or suppress host immunity. This immunomodulatory ability is likely driven by the release of hundreds of excretory/secretory proteins (ESPs) during infection. While ESPs have been shown to display immunosuppressive effects on various hosts, our understanding of the molecular interactions between individual proteins released and host immunity requires further study. We have recently identified a secreted phospholipase A2 (sPLA2) released from the entomopathogenic nematode (EPN) Steinernema carpocapsae we have named Sc-sPLA2. We report that Sc-sPLA2 increased mortality of Drosophila melanogaster infected with Streptococcus pneumoniae and promoted increased bacterial growth. Furthermore, our data showed that Sc-sPLA2 was able to downregulate both Toll and Imd pathway-associated antimicrobial peptides (AMPs) including drosomycin and defensin, in addition to suppressing phagocytosis in the hemolymph. Sc-sPLA2 was also found to be toxic to D. melanogaster with the severity being both dose- and time-dependent. Collectively, our data highlighted that Sc-sPLA2 possessed both toxic and immunosuppressive capabilities

Presentation_1_Myeloid- and epithelial-derived RELMα contribute to tissue repair following lung helminth infection.pptx

Soil-transmitted helminth (STH) infections impact billions of individuals globally; however, there is a need to clarify the long-term impacts of these infections on pulmonary health owing to their transient migration and subsequent damage to the lungs. In mouse models of these infections using Nippostrongylus brasiliensis, lung pathology persists at later time points post single infection. These studies also indicate the persistent transcriptional expression of resistin-like molecule α (RELMα), an immunomodulatory protein induced in type 2 immunity and alternatively activated macrophages. Using constitutive and tamoxifen-inducible cell-specific RELMα knockout mouse strains, we identified that epithelial- and myeloid-derived RELMα protein remained elevated at 30 days post infection and altered the immune cell signature and gene expression in lung compartments. Histopathological assessment of alveolar damage revealed a role for RELMα in tissue repair, suggesting the importance of sustained RELMα expression for lung recovery from helminth infection. Acellular three-dimensional (3D) lung scaffolds were prepared from the lungs of wild-type (WT), RELMα KO-naive, or 30 days post N. brasiliensis-infected mice to assess their ability to support epithelial cell growth. N. brasiliensis infection significantly altered the scaffold and impaired epithelial cell growth and metabolic activity, especially in the RELMα KO scaffolds. These findings underscore a need to identify the long-term impacts of helminth infection on human pulmonary disease, particularly as alveolar destruction can develop into chronic obstructive pulmonary disease (COPD), which remains among the top global causes of death. Translation of these findings to human protein resistin, with sequence homology to RELMα therapeutic opportunities in lung repair.</p