RESUMO
Helminth parasites infect over 2 billion people worldwide resulting in huge global health and economic burden. Helminths typically stimulate Type 2 immune responses and excel at manipulating or suppressing host-immune responses resulting in chronic infections that can last for years to decades. Alongside the importance for the development of helminth treatments and vaccines, studying helminth immunity has unraveled many fundamental aspects of Type 2 immunity and immune regulation with implications for the treatment of autoimmunity and Type 2-mediated diseases, such as allergies. Here we describe the maintenance and use of Litomosoides sigmodontis, a murine model for studying host-parasite interactions, Type 2 immunity, and vaccines to tissue-dwelling filarial nematodes, which in humans cause lymphatic filariasis (e.g., Brugia malayi) and onchocerciasis (Onchocerca volvulus).
Assuntos
Filariose/imunologia , Filariose/parasitologia , Filarioidea , Interações Hospedeiro-Parasita/imunologia , Imunidade , Animais , Antígenos de Helmintos/imunologia , Modelos Animais de Doenças , Feminino , Camundongos , Ácaros/parasitologiaRESUMO
Parasitic nematodes have evolved sophisticated mechanisms to communicate with their hosts in order to survive and successfully establish an infection. The transfer of RNA within extracellular vesicles (EVs) has recently been described as a mechanism that could contribute to this communication in filarial nematodes. It has been shown that these EVs are loaded with several types of RNAs, including microRNAs, leading to the hypothesis that parasites could actively use these molecules to manipulate host gene expression and to the exciting prospect that these pathways could result in new diagnostic and therapeutic strategies. Here, we review the literature on the diverse RNAi pathways that operate in nematodes and more specifically our current knowledge of extracellular RNA (exRNA) and EVs derived from filarial nematodes in vitro and within their hosts. We further detail some of the issues and questions related to the capacity of RNA-mediated communication to function in parasite-host interactions and the ability of exRNA to enable us to distinguish and detect different nematode parasites in their hosts.
Assuntos
Vesículas Extracelulares/genética , Interações Hospedeiro-Parasita/genética , MicroRNAs/genética , Nematoides/genética , RNA Interferente Pequeno/genética , Animais , Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Parasitos/genética , Interferência de RNARESUMO
Juvenile female Litomosoides sigmodontis secrete a protein (Juv-p120) highly modified with dimethylethanolamine (DMAE). In an attempt to establish the source of this decoration worms were pulsed with [3H]-choline and [3H]-ethanolamine and the radio-isotope labelled products analysed. Both isotope labels were successfully taken up by the worms, as demonstrated by labelling of phospholipids with [3H]-choline, being predominantly incorporated into phosphatidylcholine and [3H]-ethanolamine into phosphatidylethanolamine. Isotope labelling of phosphatidylethanolamine was particularly striking with the worms taking up approximately 30 times as much labelled ethanolamine as choline. It was possible to detect faint labelling of Juv-p120 with [3H]-ethanolamine after prolonged exposure periods but, unlike the situation with the phospholipids, it was much more readily labelled with [3H]-choline. When pulsing with [3H]-ethanolamine it was also possible to detect isotope-labelled phosphatidylcholine, which may ultimately account for the low levels of labelling of Juv-p120. Overall our results raise the previously unconsidered but intriguing possibility that in L. sigmodontis, choline may be the precursor of DMAE.
