The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts
Open accessAbstract
The abundant cell surface glycolipid lipophosphoglycan (LPG) was implicated in many steps of the Leishmania infectious cycle by biochemical tests. The presence of other abundant surface or secreted glycoconjugates sharing LPG domains, however, has led to uncertainty about the relative contribution of LPG in vivo . Here we used an Leishmania major lpg1 - mutant, which lacks LPG alone and shows attenuated virulence, to dissect the role of LPG in the establishment of macrophage infections in vivo. lpg1 - was highly susceptible to human complement, had lost the ability to inhibit phagolysosomal fusion transiently, and was oxidant sensitive. Studies of mouse mutants defective in relevant defense mechanisms confirmed the role of LPG in oxidant resistance but called into question the importance of transient inhibition of phagolysosomal fusion for Leishmania macrophage survival. Moreover, the limited lytic activity of mouse complement appears to be an ineffective pathogen defense mechanism in vitro and in vivo , unlike human hosts. In contrast, lpg1 - parasites bound C3b and resisted low pH and proteases normally, entered macrophages efficiently and silently, and continued to inhibit host-signaling pathways. These studies illustrate the value of mechanistic approaches focusing on both parasite and host defense pathways in dissecting the specific biological roles of complex virulence factors such as LPG.
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Cites
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Self-citationLeishmania species: models of intracellular parasitism
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Cited by
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Proteomic analysis of the secretome of Leishmania donovani
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Cysteine peptidases as virulence factors of Leishmania
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Persistence Without Pathology in Phosphoglycan-Deficient Leishmania major
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Self-citationLeishmania promastigotes: building a safe niche within macrophages
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Metadata
- Authors
- Späth, G. F., Garraway, L. A., Turco, S. J., & Beverley, S. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-07-17
- Volume
- 100
- Issue
- 16
- Pages
- 9536-9541
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2018138443
- Cited by
- 272
- References
- 39
- FWCI
- 15.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Späth, G. F., Garraway, L. A., Turco, S. J., & Beverley, S. M. (2003). The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1530604100
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