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

Content Provider	PubMed Central
Author	Hewitson, James P. Dominik, Rückerl Harcus, Yvonne Murray, Janice Webb, Lauren M. Babayan, Simon A. Allen, Judith E. Kurniawan, Agnes Maizels, Rick M.
Editor	Mitre, Edward
Copyright Year	2014
Abstract	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, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1003930
Starting Page	1003930
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	2
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2014-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

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

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

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