Dataset Information

Human macrophage polarization in the response to Mycobacterium leprae genomic DNA.

ABSTRACT: Infection with Mycobacterium leprae, the causative organism of leprosy, is still endemic in numerous parts of the world including the southwestern United States. The broad variation of symptoms in the leprosy disease spectrum range from the milder tuberculoid leprosy (paucibacillary) to the more severe and disfiguring lepromatous leprosy (multibacillary). The established thinking in the health community is that host response, rather than M. leprae strain variation, is the reason for the range of disease severity. More recent discoveries suggest that macrophage polarization also plays a significant role in the spectrum of leprosy disease but to what degree it contributes is not fully established. In this study, we aimed to analyze if different strains of M. leprae elicit different transcription responses in human macrophages, and to examine the role of macrophage polarization in these responses. Genomic DNA from three different strains of M. leprae DNA (Strains NHDP, Br4923, and Thai-53) were used to stimulate human macrophages under three polarization conditions (M1, M1-activated, and M2). Transcriptome analysis revealed a large number of differentially expressed (DE) genes upon stimulation with DNA from M. leprae strain Thai-53 compared to strains NHDP and Br4923, independent of the macrophage polarization condition. We also found that macrophage polarization affects the responses to M. leprae DNA, with up-regulation of numerous interferon stimulated genes. These findings provide a deeper understanding of the role of macrophage polarization in the recognition of M. leprae DNA, with the potential to improve leprosy treatment strategies.

SUBMITTER: Marin A

PROVIDER: S-EPMC8610329 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Mycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. In 2001, the genome of M. leprae was first described and subsequently four genotypes (1-4) and 16 subtypes (A-P) were identified providing means to study global transmission patterns for leprosy. In order to understand the role of asymptomatic carriers we investigated M. leprae carriage as well as infection in leprosy patients (n = 60) and healthy household contacts (HHC; n = 250) from Bangladesh using molecular detection of the bacterial element RLEP in nasal swabs (NS) and slit skin smears (SSS). In parallel, to study M. leprae genotype distribution in Bangladesh we explored strain diversity by whole genome sequencing (WGS) and Sanger sequencing. In the studied cohort in Bangladesh, M. leprae DNA was detected in 33.3% of NS and 22.2% of SSS of patients with bacillary index of 0 whilst in HHC 18.0% of NS and 12.3% of SSS were positive. The majority of the M. leprae strains detected in this study belonged to genotype 1D (55%), followed by 1A (31%). Importantly, WGS allowed the identification of a new M. leprae genotype, designated 1B-Bangladesh (14%), which clustered separately between the 1A and 1B strains. Moreover, we established that the genotype previously designated 1C, is not an independent subtype but clusters within the 1D genotype. Intraindividual differences were present between the M. leprae strains obtained including mutations in hypermutated genes, suggesting mixed colonization/infection or in-host evolution. In summary, we observed that M. leprae is present in asymptomatic contacts of leprosy patients fueling the concept that these individuals contribute to the current intensity of transmission. Our data therefore emphasize the importance of sensitive and specific tools allowing post-exposure prophylaxis targeted at M. leprae-infected or -colonized individuals.

Dataset Information

Human macrophage polarization in the response to Mycobacterium leprae genomic DNA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets