ABSTRACT
Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to Africa and the Arabian Peninsula, which causes diseases in humans and livestock. C-type lectin receptors (CLRs) represent a superfamily of pattern recognition receptors that were reported to interact with diverse viruses and contribute to antiviral immune responses but may also act as attachment factors or entry receptors in diverse species. Human DC-SIGN and L-SIGN are known to interact with RVFV and to facilitate viral host cell entry, but the roles of further host and vector CLRs are still unknown. In this study, we present a CLR-Fc fusion protein library to screen RVFV-CLR interaction in a cross-species approach and identified novel murine, ovine, and Aedes aegypti RVFV candidate receptors. Furthermore, cross-species CLR binding studies enabled observations of the differences and similarities in binding preferences of RVFV between mammalian CLR homologues, as well as more distant vector/host CLRs.
Subject(s)
Aedes , Rift Valley Fever , Rift Valley fever virus , Animals , Humans , Lectins, C-Type/genetics , Mammals , Mice , Mosquito Vectors/genetics , SheepABSTRACT
Toxocara canis and Toxocara cati are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of Toxocara larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses against Toxocara larvae are mostly unknown, whole-genome microarray transcription analysis was performed in cerebra and cerebella of experimentally infected C57Bl/6J mice as paratenic host model at days 14, 28, 70, 98, and 120 post-infection. Neuroinvasion of T. cati evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In T. canis-infected mice, 1039 cerebral and 2073 cerebellar DTGs were identified. Statistically significant dysregulations occurred in various pathways, including cholesterol biosynthesis, apoptosis signaling, and the Slit/Robo mediated axon guidance as well as different pathways associated with the immune and defense response. Observed dysregulations of the cholesterol biosynthesis, as well as the Alzheimer disease-amyloid secretase pathway in conjunction with previous histopathological neurodegenerative findings, may promote the discussion of T. canis as a causative agent for dementia and/or Alzheimer's disease. Furthermore, results contribute to a deeper understanding of the largely unknown pathogenesis and host-parasite interactions during NT, and may provide the basis for prospective investigations evaluating pathogenic mechanisms or designing novel diagnostic and therapeutic approaches.
ABSTRACT
C-type lectin receptors (CTLRs) are pattern recognition receptors which are important constituents of the innate immunity. However, their role has mostly been studied in humans and in mouse models. To bridge the knowledge gap concerning CTLRs of veterinary relevant species, a novel ovine CTLR hFc-fusion protein library which allows in vitro ligand identification and pathogen binding studies has been established. Its utility was tested with known ligands of corresponding murine CTLRs in ELISA- and flow cytometry based binding studies. The ovine CTLR-hFc library was subsequently used in a proof-of-principle pathogen binding study with the ruminant pathogen Mycoplasma mycoides subsp. capri. Some ovine CTLRs, such as Dendritic Cell Immunoreceptor (DCIR, Clec4a), Macrophage C-Type Lectin (MCL, Clec4d) and Myeloid Inhibitory C-Type Lectin-Like Receptor (MICL, Clec12a) were identified as possible candidate receptors whose role in Mycoplasma recognition can now be unraveled in further studies. This study thus shows the utility of this novel ovine CTLR-hFc fusion protein library to screen for CTLR/pathogen interactions.
