The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo

• DOI: 10.1371/journal.ppat.1003930
• Publication Date: 2014-02-27T23:10:17Z
• Authors: James P. Hewitson; Dominik Rückerl; Yvonne Harcus; Janice Murray; Lauren M. Webb; Simon A. Babayan; Judith E. Allen; Agnes Kurniawan; Rick M. Maizels
• Keywords: Brugia malayi; Microfilaria

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, also release suite excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, most abundant secreted protein Brugia malayi triose phosphate isomerase (TPI), glycolytic enzyme usually associated with cytosol. We now show while TPI prominent target antibody response infection, there little antibody-mediated inhibition catalytic activity polyclonal sera. generated panel twenty-three anti-TPI monoclonal antibodies and found only two were able block enzymatic activity. Immunisation jirds B. TPI, or mice homologous rodent filaria Litomosoides sigmodontis, failed induce neutralising protective immunity. In contrast, passive transfer prior implantation resulted in 60–70% reductions levels vivo both oocyte production individual females. The loss fecundity was accompanied reduced IFNγ expression CD4+ T cells higher proportion macrophages at site infection. Thus, enzymatically active plays an important role transmission cycle filarial parasites identified as potential for immunological pharmacological intervention against infections.