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Single gene control of resistance to cutaneous leishmaniasis in mice
Abstract:
A series of inbred, congenic resistant, and hybrid strains of mice were intradermally inoculated with 10(6) promastigotes of Leishmania tropica. These mice were divided into susceptible and resistant groups using the criteria of lesion size, development of metastatic foci and skin-test reactivity. At 16 weeks of infection, resistant strains A/J, DBA/1J, AKR/J, CBA/J, C3H/HeJ, NZB/BINJ, C57BL/6J, C57BL/10Sn, B10.D2, B10.129(10M), and B10.CE(30NX) had completely resolved their lesions, while susceptible SWR/J and BALB/cJ mice demonstrated large, nonhealing cutaneous lesions. In addition, BALB/cJ developed metastatic lesions on the extremities which progressively increased in size. A11 BALB/cJ and SWR/J mice died by 7 1/2 months of infection. The BALB/cJ female x C57BL/6J male F1 hybrid behaved in an intermediate fashion showing a slower expansion of cutaneous ulcers and a delayed development of metastatic foci, however, the infection ultimately proved fatal. The F2 generation could be separated into three distinct groups:resistant, intermediate, and susceptible mice with a lesion size distribution pattern in conformity with a 1:2:1 ratio. Male/female susceptibility differences were not noted. These data indicated that development of acquired resistance may be under the control of a single, autosomal gene. The gene did not appear to be H-2-, Ir-2-, or H-11-linked as is seen with Leishmania donovani infections.
Insights
Susceptibility to Leishmania tropica infection in mice is controlled by a single autosomal gene. This genetic factor influences lesion development and survival, with distinct resistant and susceptible mouse strains identified.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Leishmania tropica causes cutaneous leishmaniasis, a disease with variable clinical outcomes.
- Understanding the genetic basis of host resistance is crucial for developing effective treatments and vaccines.
Purpose of the Study:
- To investigate the genetic control of susceptibility and resistance to Leishmania tropica infection in mice.
- To identify the mode of inheritance for Leishmania tropica resistance.
Main Methods:
- Intradermal inoculation of various inbred, congenic, and hybrid mouse strains with Leishmania tropica promastigotes.
- Categorization of mice into susceptible and resistant groups based on lesion size, metastatic foci, and skin-test reactivity.
- Analysis of F1 and F2 generations to determine inheritance patterns.
Main Results:
- Resistant mouse strains resolved lesions within 16 weeks, while susceptible strains (SWR/J, BALB/cJ) developed nonhealing cutaneous and metastatic lesions, leading to mortality.
- F1 hybrids exhibited intermediate resistance, and F2 generation segregated into resistant, intermediate, and susceptible groups in a 1:2:1 ratio.
- No significant male/female differences in susceptibility were observed.
Conclusions:
- Acquired resistance to Leishmania tropica in mice is likely controlled by a single autosomal gene.
- This resistance gene is not linked to H-2, Ir-2, or H-11 loci, differentiating it from Leishmania donovani resistance mechanisms.