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Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host
T Aebischer1, S F Moody, E Handman
1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Abstract:
The persistence of Leishmania major parasites in mice resistant to infection was investigated by the polymerase chain reaction and in vitro culture methods. Parasite-specific DNA was detected in the lymph nodes, spleens, bone marrow, and livers of C57BL/6 mice 1 year after their recovery from infection. Live parasites were also recovered from these tissues (except liver tissues) and were used to establish in vitro isolates. Pulsed-field gel electrophoresis, Southern blotting, and Western blot (immunoblot) analyses showed that these isolates retained the karyotype and the phenotype of the original inoculum, including the levels of expression of gp63 and lipophosphoglycan, the two major surface molecules of Leishmania species. More importantly, these isolates were virulent and induced fatal disease when injected into susceptible BALB/c mice. Persistence was shown to be a more general phenomenon, since several different strains of mice which were resistant to L. major infection also harbored persistent parasites. The implications for the etiology of human leishmaniasis in immunocompromised individuals such as AIDS patients are discussed.
Insights
Leishmania major parasites can persist in resistant mice for over a year, remaining infectious and virulent. This finding has implications for understanding leishmaniasis in immunocompromised individuals.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Leishmania major causes leishmaniasis, a disease with varying outcomes in different mouse strains.
- Understanding parasite persistence is crucial for disease control and treatment strategies.
Purpose of the Study:
- To investigate the persistence of Leishmania major in resistant mouse models.
- To characterize the virulence and genetic stability of persistent Leishmania major isolates.
Main Methods:
- Polymerase chain reaction (PCR) for DNA detection.
- In vitro parasite culture.
- Pulsed-field gel electrophoresis (PFGE), Southern blotting, and Western blotting (immunoblotting).
Main Results:
- Leishmania major DNA and viable parasites were detected in resistant mice (C57BL/6) up to one year post-infection in lymph nodes, spleen, and bone marrow.
- In vitro isolates retained the original karyotype and phenotype, including surface molecule expression (gp63, lipophosphoglycan).
- These persistent isolates were virulent, causing fatal disease in susceptible BALB/c mice.
Conclusions:
- Leishmania major exhibits long-term persistence in resistant hosts, maintaining its virulence and genetic integrity.
- This persistence highlights potential challenges in complete parasite clearance and suggests implications for leishmaniasis in immunocompromised patients.