Leishmania major: a clone with low virulence for BALB/c mice elicits a Th1 type response and protects against infection with a highly virulent clone
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1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
BALB/c mice are highly susceptible to infection with Leishmania major and generally develop a severe, nonhealing form of disease following parasite inoculation. As opposed to protective Th1 type immune responses which develop in resistant strains of mice, BALB/c mice develop predominant Th2 type responses characterized by the production of high levels of IL-4, but only low levels of IFN-gamma. However, BALB/c mice will develop resistance and Th1 type responses following the inoculation of very low numbers of L. major promastigotes. In this study, we have examined the effects of parasite virulence on the immune response and disease phenotype in susceptible BALB/c mice. Two clones of L. major were isolated which differed with respect to their in vitro growth rates as promastigotes and their virulence for mice. One rapidly growing clone, L.m.F1, was highly virulent in BALB/c mice and produced nonhealing infections characterized by predominant Th2 type responses. In contrast, a slow-growing clone, L.m.S2, was less virulent in BALB/c mice and produced self-healing infections at parasite doses equivalent to those which produced progressive disease with the more virulent clone. Mice which healed infections with the L.m.S2 clone developed responses characterized by elevated production of IFN-gamma and were resistant to a challenge infection with the virulent L.m.F1 clone. These results suggest that the virulence of individual parasite clones may influence both the course of disease and the phenotype of the immune response which develops during infection.
Insights
Parasite virulence influences Leishmania major infection outcomes in BALB/c mice. Less virulent strains promote self-healing and resistance, while highly virulent strains cause severe, nonhealing disease.
Area of Science:
- Immunology
- Parasitology
- Infectious Disease
Background:
- BALB/c mice are susceptible to Leishmania major, developing severe, nonhealing disease with Th2 immune responses.
- Resistant mice develop protective Th1 responses, while BALB/c mice typically show high IL-4 and low IFN-gamma production.
Purpose of the Study:
- To investigate how Leishmania major parasite virulence affects immune response and disease in susceptible BALB/c mice.
- To compare the effects of virulent and less virulent parasite clones on infection outcomes.
Main Methods:
- Isolation and characterization of two Leishmania major clones with differing in vitro growth rates and mouse virulence.
- Inoculation of BALB/c mice with distinct parasite clones to assess disease progression and immune responses.
Main Results:
- A rapidly growing, highly virulent clone (L.m.F1) caused nonhealing Th2-dominant infections.
- A slow-growing, less virulent clone (L.m.S2) resulted in self-healing infections with elevated IFN-gamma production.
- Mice that healed from L.m.S2 infection became resistant to challenge with the virulent L.m.F1 clone.
Conclusions:
- Leishmania major parasite virulence is a key factor determining disease severity and immune response phenotype.
- Less virulent parasite clones can induce protective Th1 immunity and self-healing in susceptible hosts.
- Virulence variation among parasite clones impacts host-parasite interactions and infection control.