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Cathepsin-L Can Resist Lysis by Human Serum in


The interplay among host innate immunity and resistance mechanisms in African trypanosomes has a major impact on the host range of these tsetse-fly transmitted parasites, defining their ability to cause disease in humans. A genome-scale RNAi screen identified a highly restricted set of four genes that sensitise trypanosomes to human serum: those encoding the haptoglobin-haemoglobin receptor, a predicted trans-membrane channel, a lysosomal membrane-protein and the cysteine peptidase inhibitor. An analysis of the cysteine peptidases revealed cathepsin-L as the protease regulated by the inhibitor – and with the capacity to render the parasite resistant to lysis by human serum. These findings emphasise the importance of parasite factors for the delivery and stability of host toxins. They also shed light on the control of proteolysis by parasites and potential unanticipated consequences of therapies that target the parasite proteases.


Vyšlo v časopise: Cathepsin-L Can Resist Lysis by Human Serum in. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004130
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004130

Souhrn

The interplay among host innate immunity and resistance mechanisms in African trypanosomes has a major impact on the host range of these tsetse-fly transmitted parasites, defining their ability to cause disease in humans. A genome-scale RNAi screen identified a highly restricted set of four genes that sensitise trypanosomes to human serum: those encoding the haptoglobin-haemoglobin receptor, a predicted trans-membrane channel, a lysosomal membrane-protein and the cysteine peptidase inhibitor. An analysis of the cysteine peptidases revealed cathepsin-L as the protease regulated by the inhibitor – and with the capacity to render the parasite resistant to lysis by human serum. These findings emphasise the importance of parasite factors for the delivery and stability of host toxins. They also shed light on the control of proteolysis by parasites and potential unanticipated consequences of therapies that target the parasite proteases.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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