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Experimental leprosy in monkeys. II. Longitudinal serological observations in sooty mangabey monkeys
1Department of Microbiology, Tulane Regional Primate Research Center, Covington, LA, USA.
Abstract:
In this study, 11 SMM were grouped and inoculated with differing doses of SMM-origin Mycobacterium leprae (ML) between 4.5 x 10(8) and 1 x 10(9) by either combined IV/IC routes or by IV or IC route alone. The combined route was the most effective in eliciting progressive, disseminated LL leprosy. In all, 6 of 7 SMM inoculated by the combined routes developed leprosy requiring treatment at some point. Only 1 of 4 inoculated by a single route developed persisting leprosy requiring chemotherapy. Either no disease or spontaneous regression of initial disease occurred in the other 3 animals inoculated by a single route. Doses in excess of 1 x 10(9) ML were more effective than lesser doses. An association was observed between the development of IgG anti-PGL-I ELISA OD values and resistance to leprosy and between IgM anti-PGL-I and leprosy progression or susceptibility. Serum PGL-I antigen levels, determined by dot ELISA, paralleled disease severity longitudinally. High positive OD values of anti-LAM IgG prior to ML inoculation were observed in the majority of leprosy-susceptible SMM in contrast to negative levels in more resistant animals. Anti-LAM IgG OD values exceeded the positive cut-off point after inoculation in 5 of 11 SMM; 3 of these 5 had concurrent detectable serum levels of PGL-I antigen.
Insights
The combined intravenous/intracerebral route effectively induced leprosy in SMM, unlike single routes. Higher Mycobacterium leprae doses and specific antibody levels correlated with disease progression or resistance.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Leprosy, caused by Mycobacterium leprae (ML), remains a significant global health challenge.
- Understanding transmission routes and host immune responses is crucial for developing effective prevention and treatment strategies.
Purpose of the Study:
- To investigate the efficacy of different inoculation routes (intravenous/IV, intracerebral/IC, combined IV/IC) for inducing leprosy in SMM.
- To explore the correlation between ML dosage, inoculation route, and the development of leprosy.
- To examine the relationship between specific antibody responses (IgG anti-PGL-I, IgM anti-PGL-I, anti-LAM IgG) and ML antigen levels with disease progression and susceptibility in SMM.
Main Methods:
- Eleven SMM were inoculated with varying doses of ML (4.5 x 10(8) to 1 x 10(9)) via combined IV/IC, IV alone, or IC alone routes.
- Disease progression and the need for chemotherapy were monitored.
- ELISA was used to measure IgG anti-PGL-I, IgM anti-PGL-I, and anti-LAM IgG antibody levels.
- Dot ELISA was employed to quantify serum PGL-I antigen levels.
Main Results:
- The combined IV/IC inoculation route was most effective, with 6 of 7 SMM developing leprosy requiring treatment.
- In contrast, only 1 of 4 SMM inoculated via a single route developed persistent leprosy; the others showed no disease or spontaneous regression.
- Higher ML doses (> 1 x 10(9)) were more effective in disease induction.
- Elevated IgG anti-PGL-I levels correlated with leprosy resistance, while IgM anti-PGL-I correlated with progression/susceptibility.
- Serum PGL-I antigen levels paralleled disease severity.
- Pre-inoculation high anti-LAM IgG levels were associated with susceptibility, while post-inoculation increases were observed in some SMM with detectable PGL-I antigen.
Conclusions:
- The combined IV/IC route is highly effective for experimental leprosy induction in SMM.
- Specific antibody profiles (IgG anti-PGL-I, IgM anti-PGL-I, anti-LAM IgG) and antigen levels serve as potential biomarkers for leprosy susceptibility and progression.
- This study provides valuable insights into ML pathogenesis and host immune responses, aiding in the development of novel diagnostic and therapeutic approaches.