The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	James P Hewitson, Dominik Rückerl, Yvonne Harcus, Janice Murray, Lauren M Webb, Simon A Babayan, Judith E Allen, Agnes Kurniawan, Rick M Maizels
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4c54e2a2d7ba49e7807c746ad092190c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4c54e2a2d7ba49e7807c746ad092190c
record_format	dspace
spelling	oai:doaj.org-article:4c54e2a2d7ba49e7807c746ad092190c2021-11-18T06:06:56ZThe secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.1553-73661553-737410.1371/journal.ppat.1003930https://doaj.org/article/4c54e2a2d7ba49e7807c746ad092190c2014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586152/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human 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.James P HewitsonDominik RückerlYvonne HarcusJanice MurrayLauren M WebbSimon A BabayanJudith E AllenAgnes KurniawanRick M MaizelsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 2, p e1003930 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 James P Hewitson Dominik Rückerl Yvonne Harcus Janice Murray Lauren M Webb Simon A Babayan Judith E Allen Agnes Kurniawan Rick M Maizels The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
description	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.
format	article
author	James P Hewitson Dominik Rückerl Yvonne Harcus Janice Murray Lauren M Webb Simon A Babayan Judith E Allen Agnes Kurniawan Rick M Maizels
author_facet	James P Hewitson Dominik Rückerl Yvonne Harcus Janice Murray Lauren M Webb Simon A Babayan Judith E Allen Agnes Kurniawan Rick M Maizels
author_sort	James P Hewitson
title	The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
title_short	The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
title_full	The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
title_fullStr	The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
title_full_unstemmed	The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
title_sort	secreted triose phosphate isomerase of brugia malayi is required to sustain microfilaria production in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4c54e2a2d7ba49e7807c746ad092190c
work_keys_str_mv	AT jamesphewitson thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT dominikruckerl thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT yvonneharcus thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT janicemurray thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT laurenmwebb thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT simonababayan thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT juditheallen thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT agneskurniawan thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT rickmmaizels thesecretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT jamesphewitson secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT dominikruckerl secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT yvonneharcus secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT janicemurray secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT laurenmwebb secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT simonababayan secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT juditheallen secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT agneskurniawan secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo AT rickmmaizels secretedtriosephosphateisomeraseofbrugiamalayiisrequiredtosustainmicrofilariaproductioninvivo
_version_	1718424535699554304

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.

Ejemplares similares