Mycobacterium leprae alters classical activation of human monocytes in vitro. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Fallows, Dorothy; Peixoto, Blas; Kaplan, Gilla; Manca, Claudia
• Is Part Of: Journal of inflammation. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 5
• Publication Date: 2016-12
• Subjects: Mycobacterium leprae -- Polarization -- BCG vaccination -- Cytokine -- Macrophage -- Innate immunity -- Leprosy; Inflammation -- Periodicals; 616.047305
• DOI: 10.1186/s12950-016-0117-4
• Languages: English
• ISSNs: 1476-9255

Abstract

Abstract Background Macrophages play a central role in the pathogenesis of leprosy, caused byMycobacterium leprae. The polarized clinical presentations in leprosy are associated with differential immune activation. In tuberculoid leprosy, macrophages show a classical activation phenotype (M1), while macrophages in lepromatous disease display characteristics of alternative activation (M2). Bacille Calmette-Guérin (BCG) vaccination, which protects against leprosy, can promote sustained changes in monocyte response to unrelated pathogens and may preferentially direct monocytes towards an M1 protective phenotype. We previously reported thatM. leprae can dampen the response of naïve human monocytes to a strong inducer of pro-inflammatory cytokines, such as BCG. Here, we investigated the ability of the pathogen to alter the direction of macrophage polarization and the impact of BCG vaccination on the monocyte response toM. leprae . Findings We show that in vitro exposure of monocytes from healthy donors toM. leprae interferes with subsequent M1 polarization, indicated by lower levels of M1-associated cytokine/chemokines released and reduced expression of M1 cell surface markers. Exposure toM. leprae phenolic glycolipid (PGL) 1, instead of whole bacteria, demonstrated a similar effect on M1 cytokine/chemokine release. In addition, we found that monocytes from 10-week old BCG-vaccinated infants released higher levels of the pro-inflammatory cytokines TNF-α and IL-1β in response toM. leprae compared to those from unvaccinated infants. Conclusion Exposure toM. leprae has an inhibitory effect on M1 macrophage polarization, likely mediated through PGL-1. By directing monocyte/macrophages preferentially towards M1 activation, BCG vaccination may render the cells more refractory to the inhibitory effects of subsequentM. leprae infection.