Characterization of immune responses to Wolbachia in individuals with lymphatic filariasis
Punkosdy, George Albert
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Lymphatic filariasis is a parasitic disease caused by infection with the filarial nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. For some time, researchers have known that these worms harbor endosymbiotic bacterium belonging to the genus Wolbachia; however, it is not known what effect Wolbachia have on the development of the filarial disease. In order to test this hypothesis, the following studies were designed to determine whether individuals with lymphatic filariasis mount immune responses to Wolbachia. First, it was demonstrated in Brugia malayi-infected rhesus monkeys that antibodies to a major Wolbachia surface protein (WSP) were associated with the development of lymphedema and worm death. Similar results were also obtained using cross sectional serum samples from individuals living in Leogane, Haiti, an area endemic for lymphatic filariasis. In these studies, individuals with lymphedema or hydrocele had significantly higher levels of antibodies to WSP than infection- and gender-matched individuals without the chronic manifestations of the disease. In order to investigate the fate of Wolbachia following worm death, the in situ distribution of Wolbachia was assessed in granulomatous nodules collected from individuals in Recife, Brazil that developed following adult worm death. In 4/17 of these nodules, WSP staining was observed not only inside the filarial worms but also in the surrounding inflammation. In one case, Wolbachia antigen staining was observed inside human macrophages/giant cells that make up the granuloma. However, there were no differences in the histological characteristics of nodules where Wolbachia antigens staining was observed outside the worm compared to nodules where Wolbachia antigen staining was only observed inside the worm. Finally, in order to investigate whether individuals with lymphatic filariasis mount inflammatory immune responses to WSP, cytokine/chemokine responses were assayed in PBMC cultures stimulated with sWSP. In these studies, it was observed that the majority of cell cultures from individuals living in Leogane, Haiti produced the monocyte chemoattractants MCP-1 and MIP-1² in response to sWSP. Although levels of MIP-1² were similar among the different groups of Haitians, cell cultures from individuals with lymphedema produced significantly more MCP-1 than did cell cultures from individuals who were microfilaremic.