Dataset Information

Anopheles NF-?B-regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam.

ABSTRACT: Insects rely on innate immune responses controlled by the immune deficiency (IMD), Toll, and other immune signaling pathways to combat infection by a broad spectrum of pathogens. These pathways signal to downstream NF-?B family transcription factors that control specific antipathogen action via direct transcriptional control of immune effectors, hematopoiesis, and melanization. Here we show that in the Anopheles malaria vector, IMD and Toll pathways mediate species-specific defenses against Plasmodium and bacteria through the transcriptional regulation of splicing factors Caper and IRSF1 that, in turn, determine the production of pathogen-specific splice variant repertoires of the hypervariable pattern recognition receptor AgDscam. This mechanism represents an additional level of immune response regulation that may provide a previously unrecognized level of plasticity to the insect immune pathway-regulated antipathogen defenses.

SUBMITTER: Dong Y

PROVIDER: S-EPMC3614911 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anopheles NF-κB-regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam.

Dong Yuemei Y Cirimotich Chris M CM Pike Andrew A Chandra Ramesh R Dimopoulos George G

Cell host & microbe 20121001 4

Insects rely on innate immune responses controlled by the immune deficiency (IMD), Toll, and other immune signaling pathways to combat infection by a broad spectrum of pathogens. These pathways signal to downstream NF-κB family transcription factors that control specific antipathogen action via direct transcriptional control of immune effectors, hematopoiesis, and melanization. Here we show that in the Anopheles malaria vector, IMD and Toll pathways mediate species-specific defenses against Plas ...[more]

PMID: 23084919

Similar Datasets

Project description:The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR). Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM) led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING)-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG) 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR). M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

Dataset Information

Anopheles NF-?B-regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam.

Publications

Anopheles NF-κB-regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets