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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 27, 2010
Gene expression patterns associated with Leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice
Carlos M Restrepo1, Alejandro Llanes1, Lizzi Herrera1
1Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama City, Panama, Republic of Panama.
Abstract:
Leishmania parasites can trigger different host immune responses that result in varying levels of disease severity. The C57BL/6 and BALB/c mouse strains are among the host models commonly used for characterizing the immunopathogenesis of Leishmania species and the possible antileishmanial effect of novel drug candidates. C57BL/6 mice tend to be resistant to Leishmania infections, whereas BALB/c mice display a susceptible phenotype. Studying species-specific interactions between Leishmania parasites and different host systems is a key step to characterize and validate these models for in vivo studies. Here, we use RNA-Seq and differential expression analysis to characterize the transcriptomic profiles of C57BL/6 and BALB/c peritoneal-derived macrophages in response to Leishmania panamensis infection. We observed differences between BALB/c and C57BL/6 macrophages regarding pathways associated with lysosomal degradation, arginine metabolism and the regulation of cell cycle. We also observed differences in the expression of chemokine and cytokine genes associated with regulation of immune responses. In conclusion, infection with L. panamensis induced an inflammatory gene expression pattern in C57BL/6 macrophages that is more consistently associated with a classic macrophage M1 activation, whereas in BALB/c macrophages a gene expression pattern consistent with an intermediate inflammatory response was observed.
Insights
This study reveals distinct macrophage responses to Leishmania panamensis infection in C57BL/6 and BALB/c mice. C57BL/6 macrophages show M1 activation, while BALB/c exhibit an intermediate inflammatory response, impacting disease severity.
Area of Science:
- Immunology
- Parasitology
- Genomics
Background:
- Leishmania parasites induce variable host immune responses and disease severity.
- C57BL/6 (resistant) and BALB/c (susceptible) mice are key models for Leishmania research.
- Understanding host-parasite interactions is crucial for validating these models.
Purpose of the Study:
- To characterize transcriptomic profiles of C57BL/6 and BALB/c macrophages upon Leishmania panamensis infection.
- To identify differences in host immune responses between resistant and susceptible mouse strains.
Main Methods:
- RNA-sequencing (RNA-Seq) was employed to analyze gene expression.
- Differential expression analysis was performed on peritoneal-derived macrophages.
- Comparative transcriptomics between C57BL/6 and BALB/c macrophages were conducted.
Main Results:
- Significant differences were observed in pathways related to lysosomal degradation, arginine metabolism, and cell cycle regulation.
- Distinct expression patterns of chemokine and cytokine genes involved in immune response regulation were identified.
- C57BL/6 macrophages displayed an M1-like inflammatory gene expression profile, while BALB/c showed an intermediate inflammatory response.
Conclusions:
- Leishmania panamensis infection elicits strain-specific transcriptomic responses in mouse macrophages.
- These findings highlight the utility of C57BL/6 and BALB/c models in studying Leishmania immunopathogenesis.
- The observed differences provide insights into the molecular mechanisms underlying varying disease susceptibility.
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