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Trypanosoma brucei distribution in the male reproductive system

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Resumo:Trypanosoma brucei is the causative agent of Human African trypanosomiasis, also known as sleeping sickness. Disease progression usually begins with a haemolympathic phase, followed by parasite invasion of the central nervous system. Currently no vaccines are available and a limited range of drugs exists to treat this disease, many of them associated with high toxicity. Recent studies have revealed the presence of trypanosomes in the male reproductive system. When considering trypanocidal drug development reproductive organs are of interest, since parasites that infiltrate and persist in the male gonads may be protected from drugs by the blood-testis barrier. Since there is epidemiological evidence in humans for the sexual transmission of T. brucei, understanding if and how trypanosomes are distributed in the male reproductive system may also help identifying the pathways underlying sexual transmission of the disease. Here we characterized the infection in the mouse male reproductive system using an animal model and showed, through histological analysis, parasites and inflammatory cells infiltrating the male reproductive system later in the infection, especially in the epididymis. Parasite density, determined by quantitative PCR of genomic DNA, confirmed that parasite load increased overtime. Transmission electron microscopy showed that even when found in higher numbers, trypanosomes in the epididymis had severe morphological changes consistent with cell death, possibly due to the immune response seen later on. Overall, we propose that the inflammatory cell infiltration may compromise drug diffusion, enabling reproductive organs to act as a reservoir for parasites. Also, parasite distribution in epididymis may enable sexual transmission. The identification of this reservoir opens new pathways to future research concerning parasite tropism and development of new and more efficient drugs.
Autores principais:Silva, Sílvia Maria de Jesus Pimenta Teixeira da
Assunto:Tripanossomíase humana africana Sistema reprodutor masculino Transmissão sexual Modelos animais Histologia
Ano:2017
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa

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