02280nas a2200265   4500000000100000008004100001260001200042653001200054653002800066653002500094653001100119100001200130700001500142700001400157700001100171700001100182700001100193700001600204245008700220856007000307300001100377490000600388520160600394022001402000       2021                            d  c12/202110aleprosy10aMacrophage polarization10aMycobacterium leprae10aRNAseq1 aMarin A1 aVan Huss K1 aCorbett J1 aKim SJ1 aMohl J1 aHong B1 aCervantes J00aHuman macrophage polarization in the response to Mycobacterium leprae genomic DNA.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610329/pdf/main.pdf  a1000150 v23 a<p>Infection with 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 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 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 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 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 DNA, with the potential to improve leprosy treatment strategies.</p>
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