%0 Journal Article
%T Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function
%A Natalia Gomez-Escobar
%A Clare Bennett
%A Lidia Prieto-Lafuente
%A Toni Aebischer
%A Clare C Blackburn
%A Rick M Maizels
%J BMC Biology
%D 2005
%I BioMed Central
%R 10.1186/1741-7007-3-8
%X To test the hypothesis that ALT proteins modulate host immunity, we adopted an alternative transfection strategy to express these products in the protozoan parasite Leishmania mexicana. We then followed the course of infection in vitro in macrophages and in vivo in mice. Expression of ALT proteins, but not a truncated mutant, conferred greater infectivity of macrophages in vitro, reaching 3-fold higher parasite densities. alt-transfected parasites also caused accelerated disease in vivo, and fewer mice were able to clear infection of organisms expressing ALT. alt-transfected parasites were more resistant to IFN-¦Ã-induced killing by macrophages. Expression profiling of macrophages infected with transgenic L. mexicana revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, both associated with the Th2-type response observed in in vivo filarial infection.Leishmania transfection is a tractable and informative approach to determining immunological functions of single genes from heterologous organisms. In the case of the filarial ALT proteins, our data suggest that they may participate in the Th2 bias observed in the response to parasite infection by modulating cytokine-induced signalling within immune system cells.Pathogens have evolved many ingenious mechanisms to manipulate innate and adaptive host immune responses [1-6]. The nematode parasite Brugia malayi is a causative agent of the disease lymphatic filariasis, which afflicts over 100 million people in tropical countries. Mosquito-borne infective stage larvae gain entry to the human body during a blood meal, and establish long-lived infections characterised by down-regulation of host T cell and macrophage reactivity [7,8]. We have studied the profile of genes expressed in infective larvae and reported that ~5% of the mRNA transcripts from this stage correspond to two closely related genes, which we have named abundant larval transcript (alt) -1 and -2 [9,10]. The two genes encode proteins with 79% amin
%U http://www.biomedcentral.com/1741-7007/3/8