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Persistence without pathology in phosphoglycan-deficient Leishmania major
Gerald F Späth1, Lon-Fey Lye, Hiroaki Segawa
1Department of Molecular Microbiology, Washington University Medical School, St. Louis, MO 63110, USA.
Abstract:
Leishmania infections involve an acute phase of replication within macrophages, typically associated with pathology. After recovery parasites persist for long periods, which can lead to severe disease upon reactivation. Unlike the role of host factors, parasite factors affecting persistence are poorly understood. Leishmania major lacking phosphoglycans (lpg2-) were unable to survive in sand flies and macrophages, but retained the ability to persist indefinitely in the mammalian host without inducing disease. The L. major lpg2- thus provides a platform for probing parasite factors implicated in persistence and its role in disease and immunity.
Insights
Leishmania parasites lacking phosphoglycans can persist long-term in hosts without causing disease. This discovery offers a new model for studying parasite persistence and its role in Leishmania immunity.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Leishmania infections cause acute pathology via macrophage replication.
- Parasite persistence after recovery can lead to severe disease upon reactivation.
- Factors influencing Leishmania persistence are poorly understood, especially parasite-derived factors.
Purpose of the Study:
- To investigate the role of parasite factors in Leishmania persistence and disease.
- To characterize Leishmania major lacking phosphoglycans (lpg2-) for persistence studies.
Main Methods:
- Generation and characterization of Leishmania major mutant lacking phosphoglycans (lpg2-).
- Assessment of parasite survival in sand flies and macrophages.
- Evaluation of long-term persistence in mammalian hosts.
Main Results:
- Leishmania major lpg2- mutants were unable to survive in sand flies and macrophages.
- Despite impaired survival in vectors and hosts, lpg2- mutants persisted indefinitely in the mammalian host.
- The lpg2- mutant did not induce disease in the mammalian host.
Conclusions:
- Leishmania phosphoglycans are essential for survival in sand flies and macrophages but not for long-term host persistence.
- Leishmania major lpg2- mutants provide a valuable model for studying parasite persistence independent of acute pathology.
- This model can be used to investigate parasite factors controlling persistence and their impact on host immunity.
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