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IS-BILAT-Mobilitet Norge-USA /Canada

Assessing a role for age and puberty in the immune-mediated persistence of female genital lesions in human S. haematobium infection

Tildelt: kr 80 000

Schistosoma haematobium (Sh) infection of the female genital tract, known as female genital schistosomiasis (FGS), induces genital lesions that are heavily infiltrated with macrophages and other immune cells. While the drug praziquantel effectively clears the parasitic infection, it is ineffective at resolving the associated genital lesions in adult women. Interestingly, when the same drug is given during childhood or adolescence, the genital lesions do resolve following parasite clearance. Thus, there se ems to be a switch that happens after sexual maturation that diverts the normal wound healing pathways toward pathways that result instead in intractable fibrosis. Here we propose to examine potential mechanisms underlying this switch. First we will dete rmine, by a quantitative RT-PCR panel, expression profiles of 8 genes involved in fibrosis and wound healing. We will perform this analysis in urine and blood samples collected from both children and adults with FGS pre- and post-praziquantel treatment. A dditionally, we will do a similar analysis on vaginal lavage samples from the adults in the cohort only. Obtaining a molecular signature of the expression patterns of these genes pre- and post-treatment will provide a good indication of which pathways are active in resolution or persistence of FGS lesions in response to treatment in the two age groups. Secondly, we will develop a cell culture system to scrutinize the phenotype of monocyte-derived macrophages isolated from FGS patients and exposed to Sh a ntigens. Since macrophages are known to be modulated by female sex hormones, we will test if the addition of sex hormones, such as those that become highly active in puberty and beyond, modulate the phenotype of the macrophages in culture. Finally, we wil l try to corroborate our in vitro findings with a small pilot study to phenotype tissue macrophages isolated from vaginal lavages of women with FGS, and attempt to correlate phenotype with hormone levels.

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IS-BILAT-Mobilitet Norge-USA /Canada

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