Coordinate uptake of mycobacteria sand oxLDL by differential expression of IL‐10 and IL‐15 derived CD209+ macrophage subsets in human leprosy

Abstract

Macrophage differentiation and function were investigated in the context of leprosy, which presents as a clinical and immunologic spectrum. The disseminated lepromatous (L‐lep) form is filled with lipid‐laden macrophages and numerous mycobacteria, while the localized tuberculoid form has macrophages but no mycobacteria found. Th1 macrophages correspond to T‐lep and can be derived in vitro with IL‐15. We hypothesized that the Th2 cytokine, IL‐10, can lead to CD209+ macrophage differentiation correlating to L‐lep macrophage phenotype and function. IL‐10 derived macrophages (M10) were found to express CD209 and CD163 in contrast to M15 being CD209+CD163−. M10 were determined to be highly endocytic by multiple assays and phagocytose more mycobacteria than IL‐15 derived macrophages (M15). Furthermore, M10 efficiently take in oxidized LDL (oxLDL) and become foam cell macrophages. Macrophage subsets in leprosy lesions were analyzed and we found CD209+CD163+ M10 macrophages in L‐lep lesions, while CD209+CD163− M15 macrophages were found in T‐Lep lesions. Furthermore, CD163+ macrophages in lepromatous leprosy lesions harbored mycobacteria and apolipoprotein B, a component of oxLDL, suggesting that M10 macrophage subset may lead to foam cell formation and mycobacterial uptake the pathogenesis of leprosy.