Gene expression patterns associated with Leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice

Author summary Leishmaniasis is a disease caused by parasites of the Leishmania genus. Leishmania panamensis is a species that causes cutaneous leishmaniasis and potentially the more severe mucocutaneous leishmaniasis characterized by disfiguring lesions in nose and mouth. The C57BL/6 and BALB/c mouse strains are among the models commonly used for studying Leishmania infection and evaluating the effect of novel drug candidates. Previous research shows that the response of these two strains to Leishmania infection differs by factors that are related to both mouse strain genetic background and the infecting Leishmania species. In this study we characterized the differences in gene expression in macrophages of both mouse strains using next generation sequencing technologies. We identified differences in the expression of genes associated with the immune response that suggest that C57BL/6 macrophages display a classical pattern of activation associated with resolution of the disease, while BALB/c macrophages show an intermediate pattern of activation that favors parasite persistence and chronicity of the disease. The intermediate pattern observed in BALB/c macrophages resembles that observed in human infections with L. panamensis and supports the use of BALB/c as the preferred model for studying L. panamensis infection. 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.

Automated summary

Leishmaniasis is a disease caused by parasites, with different mouse strains exhibiting varying responses to Leishmania infection. By studying gene expression differences in macrophages, it was found that C57BL/6 macrophages display a classical activation pattern associated with disease resolution, whereas BALB/c macrophages show an intermediate activation pattern favoring parasite persistence. The intermediate pattern observed in BALB/c macrophages resembles the pattern seen in human infections with L. panamensis, supporting BALB/c as a preferred model for studying L. panamensis infection.