scholarly journals 20-hydroxyecdysone (20E) primes innate immune responses that limit bacteria and malaria parasite survival in Anopheles gambiae

2019 ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Ryan C. Smith
Keyword(s):  
Immune Function ◽  
Anopheles Gambiae ◽  
Blood Feeding ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Temporal Regulation ◽  
Immune Genes ◽  
Pathogen Challenge ◽  
Immunological Effects ◽  
Cellular Immune

AbstractBlood-feeding is an integral behavior of mosquitoes to acquire nutritional resources needed for reproduction. This requirement also enables mosquitoes to serve as efficient vectors to acquire and potentially transmit a multitude of mosquito-borne diseases, most notably malaria. Recent studies suggest that mosquito immunity is stimulated following a blood meal, independent of infection status. Since blood-feeding results in the increased production of the hormone 20-hydroxyecdysone (20E), we hypothesized that 20E may play an important role in priming the immune response for pathogen challenge. Herein, we examine the immunological effects of priming in Anopheles gambiae with 20E prior to pathogen infection, demonstrating a significant reduction in bacteria and Plasmodium berghei survival in the mosquito host. RNA-seq analysis following 20E treatment identifies several known 20E-regulated genes, as well as several immune genes with previously reported function in anti-pathogen defense. This includes the anti-microbial peptide cecropin 3, which we demonstrate its role as an antagonist of bacteria and Plasmodium in Anopheles gambiae and provide support that these responses are under temporal regulation. Together, these data demonstrate that 20E influences cellular immune function and anti-pathogen immunity following mosquito blood-feeding, arguing the importance of hormones in the regulation of mosquito innate immune function.

scholarly journals 20-Hydroxyecdysone Primes Innate Immune Responses That Limit Bacterial and Malarial Parasite Survival in Anopheles gambiae

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Ryan C. Smith
Keyword(s):  
Immune Function ◽  
Anopheles Gambiae ◽  
Blood Meal ◽  
Egg Production ◽  
Blood Feeding ◽  
Innate Immune ◽  
Content Type ◽  
Innate Immune Function ◽  
Cellular Immune Function ◽  
Cellular Immune

ABSTRACT Blood feeding is an integral behavior of mosquitoes to acquire nutritional resources needed for reproduction. This requirement also enables mosquitoes to serve as efficient vectors to acquire and potentially transmit a multitude of mosquito-borne diseases, most notably malaria. Recent studies suggest that mosquito immunity is stimulated following a blood meal, independent of infection status. Since blood feeding promotes production of the hormone 20-hydroxyecdysone (20E), we hypothesized that 20E plays an important role in priming the immune response for pathogen challenge. Here, we examine the immunological effects of priming Anopheles gambiae with 20E prior to pathogen infection, demonstrating a significant reduction in bacteria and Plasmodium berghei survival in the mosquito host. Transcriptome sequencing (RNA-seq) analysis following 20E treatment identifies several known 20E-regulated genes, as well as several immune genes with previously reported function in antipathogen defense. Together, these data demonstrate that 20E influences cellular immune function and antipathogen immunity following mosquito blood feeding, arguing the importance of hormones in the regulation of mosquito innate immune function. IMPORTANCE Blood feeding is required to provide nutrients for mosquito egg production and serves as a mechanism to acquire and transmit pathogens. Shortly after a blood meal is taken, there is a peak in the production of 20-hydroxyecdysone (20E), a mosquito hormone that initiates physiological changes, including yolk protein production and mating refractoriness. Here, we examine additional roles of 20E in the regulation of mosquito immunity, demonstrating that priming the immune system with 20E increases mosquito resistance to pathogens. We identify differentially expressed genes in response to 20E treatment, including several involved in innate immune function as well as lipid metabolism and transport. Together, these data argue that 20E stimulates mosquito cellular immune function and innate immunity shortly after blood feeding.

scholarly journals MicroRNAs from Snellenius manilae bracovirus regulate innate and cellular immune responses of its host Spodoptera litura

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cheng-Kang Tang ◽  
Chih-Hsuan Tsai ◽  
Carol-P. Wu ◽  
Yu-Hsien Lin ◽  
Sung-Chan Wei ◽  
...  
Keyword(s):  
Immune Responses ◽  
Spodoptera Litura ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Sequencing Analysis ◽  
Innate Immune Responses ◽  
Cellular Immune Responses ◽  
Next Generation Sequencing Analysis ◽  
Cellular Immune ◽  
Generation Sequencing

AbstractTo avoid inducing immune and physiological responses in insect hosts, parasitoid wasps have developed several mechanisms to inhibit them during parasitism, including the production of venom, specialized wasp cells, and symbioses with polydnaviruses (PDVs). These mechanisms alter the host physiology to give the wasp offspring a greater chance of survival. However, the molecular mechanisms for most of these alterations remain unclear. In the present study, we applied next-generation sequencing analysis and identified several miRNAs that were encoded in the genome of Snellenius manilae bracovirus (SmBV), and expressed in the host larvae, Spodoptera litura, during parasitism. Among these miRNAs, SmBV-miR-199b-5p and SmBV-miR-2989 were found to target domeless and toll-7 in the host, which are involved in the host innate immune responses. Microinjecting the inhibitors of these two miRNAs into parasitized S. litura larvae not only severely decreased the pupation rate of Snellenius manilae, but also restored the phagocytosis and encapsulation activity of the hemocytes. The results demonstrate that these two SmBV-encoded miRNAs play an important role in suppressing the immune responses of parasitized hosts. Overall, our study uncovers the functions of two SmBV-encoded miRNAs in regulating the host innate immune responses upon wasp parasitism.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

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.

scholarly journals Roles of Shiga Toxins in Immunopathology

Toxins ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 212 ◽  
Author(s):  
Moo-Seung Lee ◽  
Vernon Tesh
Keyword(s):  
Immune Responses ◽  
Stress Responses ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Shiga Toxins ◽  
Shigella Species ◽  
Lethal Complications ◽  
Uremic Syndrome ◽  
Cellular Immune

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Notably, Stxs are not only potent inducers of cell death, but also activate innate immune responses that may lead to inflammation, and these effects may increase the severity of organ injury in patients infected with Stx-producing bacteria. In the intestines, kidneys, and central nervous system, excessive or uncontrolled host innate and cellular immune responses triggered by Stxs may result in sensitization of cells to toxin mediated damage, leading to immunopathology and increased morbidity and mortality in animal models (including primates) and human patients. Here, we review studies describing Stx-induced innate immune responses that may be associated with tissue damage, inflammation, and complement activation. We speculate on how these processes may contribute to immunopathological responses to the toxins.

scholarly journals The 20-hydroxyecdysone agonist, halofenozide, promotes anti-Plasmodium immunity in Anopheles gambiae via the ecdysone receptor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Thiago Luiz Alves e Silva ◽  
Janet Olivas ◽  
Joel Vega-Rodriguez ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Parasite ◽  
Vector Competence ◽  
Direct Injection ◽  
Blood Feeding ◽  
Mosquito Vector ◽  
Ecdysone Receptor ◽  
Principal Role ◽  
Cellular Immune

AbstractMosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.

scholarly journals Baby’s First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation

2020 ◽  
Vol 204 (9) ◽  
pp. 2380-2391 ◽  
Author(s):  
Dominika Swieboda ◽  
Erica L. Johnson ◽  
Jacob Beaver ◽  
Lisa Haddad ◽  
Elizabeth Ann L. Enninga ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Cell Phenotype ◽  
Innate Immune Responses ◽  
Temporal Regulation

scholarly journals Mosquito Phenoloxidase and Defensin Colocalize in Melanization Innate Immune Responses

2005 ◽  
Vol 53 (6) ◽  
pp. 689-698 ◽  
Author(s):  
Julián F. Hillyer ◽  
Bruce M. Christensen
Keyword(s):  
Immune Responses ◽  
Micrococcus Luteus ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Melanin Biosynthesis ◽  
Immune Reactions ◽  
Transmission Electron ◽  
Cellular Immune ◽  
Rate Limiting

Mosquitoes mount strong humoral and cellular immune responses against foreign organisms. Two components of the mosquito immune response that have received much attention are the phenoloxidase cascade that leads to melanization and antimicrobial peptides. The purpose of the current study was to use immunocytochemistry and transmission electron microscopy to identify the location of the melanization rate-limiting enzyme phenoloxidase and the antimicrobial peptide defensin in innate immune reactions against Escherichia coli and Micrococcus luteus by the mosquito Aedes aegypti. Our results show that both phenoloxidase and defensin are present at the sites of melanin biosynthesis in immune reactions against bacteria. Furthermore, both proteins are often present inside the same melanotic capsules. When hemocytes were analyzed, phenoloxidase was present in the cytosol of oenocytoids, but no significant amounts of defensin were detected inside any hemocytes. In summary, these data show that phenoloxidase and defensin colocalize in melanization reactions against bacteria and argue for further studies into the potential role of defensin in phenoloxidase-based melanization innate immune responses in mosquitoes.

scholarly journals The 20-hydroxyecdysone agonist, halofenozide, promotes anti-Plasmodium immunity in Anopheles gambiae via the ecdysone receptor

2020 ◽  
Author(s):  
Rebekah A. Reynolds ◽  
Hyeogsun Kwon ◽  
Thiago Luiz Alves e Silva ◽  
Janet Olivas ◽  
Joel Vega-Rodriguez ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Parasite ◽  
Vector Competence ◽  
Direct Injection ◽  
Blood Feeding ◽  
Mosquito Vector ◽  
Ecdysone Receptor ◽  
Principal Role ◽  
Cellular Immune

AbstractMosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.

scholarly journals Trained Immunity in Anopheles gambiae: Antibacterial Immunity Is Enhanced by Priming via Sugar Meal Supplemented With a Single Gut Symbiotic Bacterial Strain

2021 ◽  
Vol 12 ◽  
Author(s):  
Aditi Kulkarni ◽  
Ashmita Pandey ◽  
Patrick Trainor ◽  
Samantha Carlisle ◽  
Jainder S. Chhilar ◽  
...  
Keyword(s):  
Immune System ◽  
Anopheles Gambiae ◽  
Innate Immune ◽  
Rna Seq ◽  
Immune Genes ◽  
Trained Immunity ◽  
Three Samples ◽  
Immune Enhancement ◽  
Injury Control ◽  
Basal Immunity

Mosquitoes have evolved an effective innate immune system. The mosquito gut accommodates various microbes, which play a crucial role in shaping the mosquito immune system during evolution. The resident bacteria in the gut microbiota play an essential role in priming basal immunity. In this study, we show that antibacterial immunity in Anopheles gambiae can be enhanced by priming via a sugar meal supplemented with bacteria. Serratia fonticola S1 and Enterobacter sp. Ag1 are gut bacteria in mosquitoes. The intrathoracic injection of the two bacteria can result in an acute hemocoelic infection in the naïve mosquitoes with mortality of ∼40% at 24 h post-infection. However, the Enterobacter orSerratia primed mosquitoes showed a better 24 h survival upon the bacterial challenge. The priming confers the protection with a certain degree of specificity, the Enterobacter primed mosquitoes had a better survival upon the Enterobacter but not Serratia challenge, and the Serratia primed mosquitoes had a better survival upon the Serratia but not Enterobacter challenge. To understand the priming-mediated immune enhancement, the transcriptomes were characterized in the mosquitoes of priming as well as priming plus challenges. The RNA-seq was conducted to profile 10 transcriptomes including three samples of priming conditions (native microbiota, Serratia priming, and Enterobacter priming), six samples of priming plus challenges with the two bacteria, and one sample of injury control. The three priming regimes resulted in distinctive transcriptomic profiles with about 60% of genes affected by both bacteria. Upon challenges, different primed mosquitoes displayed different transcriptomic patterns in response to different bacteria. When a primed cohort was challenged with a heterogenous bacterium, more responsive genes were observed than when challenged with a homogenous bacterium. As expected, many canonical immune genes were responsive to the priming and challenge, but much more non-immune genes with various functions were also responsive in the contexts, which implies that the prior priming triggers a delicately coordinated systemic regulation that results in an enhanced immunity against the subsequent challenge. Besides the participation of typical immune pathways, the transcriptome data suggest the involvement of lysosome and metabolism in the context. Overall, this study demonstrated a trained immunity via priming with bacteria in diet.

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