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Expression data from CD4+IL-4gfp+ Th2 cells isolated from BALB/c IL-4gfp 4get mice infected with the filarial nematode Litomosoides sigmodontis.

ABSTRACT: Litomosoides sigmodontis is parasitic filarial nematode that can infect mice, and is used as a murine model for human filariasis. Type 2 immune responses are protective, but infection is typically chronic due to a combination of immune suppression by the parasite and immune regulation by the host dampening protective Type 2 immunity. We have shown that the CD4+ Th2 cells develop an intrinsically hyporesponsive or dysfunctional phenotype between day 20 and 60 of infection, denoted by an impaired ability to proliferate and produce Th2 cytokines. The hyporesponsive phenotype is PD-1/PD-L2 dependent, and impairs parasite killing (van der Werf et al. 2013. PloS Path. e1003215). This study aimed to investigate the mRNA expression of the intrinsically-hyporesponsive Th2 cells to determine the mechanisms by which they become dysfunctional, and to test whether Th2 cell intrinsic hyporesponsiveness has similarities with other forms of T cell-intrinsic regulation such as exhaustion, tolerance or anergy.

ORGANISM(S): Mus musculus

PROVIDER: GSE114308 | GEO | 2019/11/25

REPOSITORIES: GEO

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Project description:Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of approximately 6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained because the human-parasitic species cannot complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature first-stage larvae (microfilariae), released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterised members of the transthyretin-like protein family. Furthermore, biotin labelling revealed that redox proteins and enzymes involved in purinergic signalling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human–infective filarial nematode Brugia malayi (reported previously in three independent published studies) identified differences that suggest a considerable underlying diversity of potential immunomodulators. The molecules identified in L. sigmodontis excretory-secretory products show promise not only for vaccination against filarial infections, but for the amelioration of allergy and autoimmune diseases.

Dataset Information

Expression data from CD4+IL-4gfp+ Th2 cells isolated from BALB/c IL-4gfp 4get mice infected with the filarial nematode Litomosoides sigmodontis.

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