Trypanosoma brucei triggers a marked immune response in male reproductive organs

Abstract

African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei, transmitted between mammals by the bite of a tsetse. It has been recently shown that parasites accumulate in large numbers in various organs and tissues, including the mouse testis. Whether parasites are protected from the immune system in the male reproductive organ or can be transmitted through sexual route remains unknown. Here we show that parasites can be detected by fine needle aspiration cytology of the male reproductive system in mice, and histopathological analysis revealed that T. brucei accumulates in the stroma of the epididymis, epididymal adipose tissue and fibrous tunics of the testis. No parasites were found in the lumen of intact epididymal ducts or seminiferous tubules of the testis, indicating that the large majority of the parasites are not located in immune-privileged sites. In fact, these parasites are associated with marked inflammatory cell infiltration, parasite degeneration, and severe tissue damage and rupture of epididymal ducts, which may be related with reduced fertility. Overall, we show that just like in the bloodstream and most other tissues, in the male reproductive organs, T. brucei are exposed to a strong immune response. The detection of a very high number of parasites in this organ and its accessibility opens the possibility of using fine needle aspiration cytology as a complementary diagnostic tool in Animal African Trypanosomiasis.

Noninvasive Biological Samples to Detect and Diagnose Infections due to Trypanosomatidae Parasites: A Systematic Review and Meta-Analysis

“…Histological lesions characterized by testicular degeneration, epididymitis, and epididymal epithelial hyperplasia were detected in the same animals and suggest the participation of the parasite in the etiopathogenic mechanism of reproductive damage, frequently reported in infected animals [308,310,314]. In experimentally infected mice, bioluminescent imaging confirmed the localization of viable trypanosomes in infected mice [315] with an accumulation in the epididymal adipose tissue and in the epididymis [316].…”

Alternative oxidase inhibitors: Mitochondrion‐targeting as a strategy for new drugs against pathogenic parasites and fungi

“…126 In contrast, the benzoate derivatives with a larger alkyl substituent (R 1 ) are expected to bind AOX in a different way, with the ester alkyl chain pointing outward from the active site ( Figure 11B). In this series, the K i decreases as the length of R 1 increases (Figure 10, 102-115; Figure 11A, [130][131][132][133][134][135][136][137][138][139][140][141][142][143][144]. Submicromolar inhibitors were obtained when the alkyl chain was greater than or equal to C6 (141)(142)(143)(144) values ( Figure 11A).…”

“…The drug‐associated factors include high therapeutic dosages, low solubilities, the toxicity of the compounds at high dose, and their pharmacokinetics (blood concentration of SHAM and glycerol declines rapidly). The parasite‐related factors are (1) the level of parasitemia before commencement of treatment, (2) ability of the parasites to exist in both monomorphic and pleomorphic forms, and (3) abilities of the parasites to reversibly migrate from the circulation to other niches and organs such as the brain, testes, and adipose tissue …”

“…The parasite-related factors are (1) the level of parasitemia before commencement of treatment, (2) ability of the parasites to exist in both monomorphic and pleomorphic forms, and (3) abilities of the parasites to reversibly migrate from the circulation to other niches and organs such as the brain, testes, and adipose tissue. [131][132][133] The therapeutic dosage of SHAM plus glycerol is impractically and dangerously high. Van der Meer et al 134 reported that doses of 355 mg/kg SHAM plus 1216 mg/kg body weight glycerol, respectively, which resulted in plasma concentrations of 2 and 20 mM, respectively, cleared T. vivax parasitaemia in goats but had severe toxic effects, including the deaths of some of the treated animals.…”

Intravital imaging of host‐parasite interactions in organs of the thoracic and abdominopelvic cavities

“…Infectious diseases are amongst the most frequent causes for male and female reproductive pathology and infertility, in humans and animals (Bennett, Dolin, & Blaser, ; Maxie, ). Reproductive tissue tropism has been studied in the context of Trichomonas (Parsonson, Clark, & Dufty, ) , T. gondii (Lopes et al, ; Stahl, Kaneda, Tanabe, & Kumar, ), T. cruzi (Id Boufker, Alexandre, Carlier, & Truyens, ), T. brucei (Carvalho et al, ), Plasmodium (Muehlenbein, Alger, Cogswell, James, & Krogstad, ; Raji, Akinsomisoye, & Azeez, ) , Entamoeba (reviewed in [Antony and Lopez‐Po ]) and to a large extend in Leishmania (Assis, Ribeiro, Rachid, Castro, & Valle, ; Blickstein, Dgani, & Lifschitz‐Mercer, ; Cabello, Caraballo, & Millan, ; Diniz et al, ; Gonzalez, Gallego, Castaño, & Rueda, ; Mir, Fontaine, Reyes‐Gomez, Carlus, & Fontbonne, ; Schubach, Cuzzi‐Maya, Gonçalves‐Costa, Pirmez, & Oliveira‐Neto, ). Infertility can be directly associated with presence of parasites in the tissue, through triggering inflammation and tissue damage or indirectly due to systemic effects that result in impaired reproductive function.…”