Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

Abstract

Filarial nematodes are metazoan parasites with genome sizes of> 100 million base pairs, probably encoding 15 000-20 000 genes. Within this considerable gene complement, it seems likely that filariae have evolved a spectrum of immune evasion products which underpin their ability to live for many years within the human host. Moreover, no suitable vaccine currently exists for human filarial diseases, and few markers have yet been established for diagnostic use. In this review, we bring together biochemical and immunological data on prominent filarial proteins with the exciting new information provided by the Filarial Genome Project's expressed sequence tag (EST) database. In this discussion, we focus on those genes with the highest immunological profile, such as inhibitors of host enzymes, cytokine homologues and stage-specific surface proteins, as well as products associated with the mosquito-borne infective larva which offer the best opportunity for an anti-filarial vaccine. These gene products provide a fascinating glimpse of the molecular repertoire which helminth parasites have evolved to manipulate and evade the mammalian immune response.

Characterization of a Novel Filarial Serine Protease Inhibitor, Ov-SPI-1, from Onchocerca volvulus, with Potential Multifunctional Roles during Development of the Parasite

“…Moreover, it is possible that, like other previously characterized nematode protease inhibitors, such as the cystatin family (29,30) and the serpin family of serine protease inhibitors (27,28,92), the Ov-SPIs have exogenous as well as endogenous functions during the lifecycle of the parasite. This could involve the control of both host and parasite ectoproteases.…”

Differential Cytokine and Antibody Responses to Adult and Larval Stages ofOnchocerca volvulusConsistent with the Development of Concomitant Immunity

“…In the present study, IL-10 levels were high in most cases, especially in response to FOvAg; however, in initial studies (data not shown), we found that neutralization of IL-10 had no effect on IFN-␥ (or IL-5) production by PBMCs from INF individuals in response to F-OvAg. Thus, IL-10 is unlikely to be the only factor responsible for the downregulation of T-cell responses in filariasis; parasite-derived immunoregulatory molecules may also be important (33).…”

Identification and analysis of genes expressed in the adult filarial parasitic nematode Dirofilaria immitis

“…Blood in the host contains large quantities of free inorganic iron and the common biological iron chelator haem, both of which are known to be potent generators of reactive oxygen species (Tappel, 1955;Halliwell and Gutteridge, 1999). In addition, cytotoxic responses by the host immune system also contribute to the formation of damaging free radicals (Selkirk et al, 1998;Maizels et al, 2001), making oxidative stress an obvious threat to parasites such as adult D. immitis. Currently, at least two interrelated strategies have been discovered in diminishing oxidative stress in general: antioxidant enzymes to detoxify damaging free radicals directly and molecular chaperones, such as small heat shock proteins and Hsp70, to protect target proteins by covering sensitive sites or helping with refolding (Papp et al, 2003).…”