Research ArticleImmunology

Lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils

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Science Signaling  11 Oct 2016:
Vol. 9, Issue 449, pp. ra101
DOI: 10.1126/scisignal.aaf1585

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Escaping the lysosomal death path

Macrophages and neutrophils bind to and internalize microbes within endocytic organelles called phagosomes. Fusion of phagosomes with lysosomes destroys the microbe. Pathogenic mycobacteria, such as Mycobacterium tuberculosis, prevent phagosomal maturation and lysosomal fusion and thus survive and replicate within the host cell. Nakayama et al. found that mycobacterial membrane glycolipids called lipoarabinomannans (LAMs) of both pathogenic and nonpathogenic strains of mycobacteria were similarly efficient at binding to lactosylceramide (LacCer) in the plasma membrane lipid rafts of human neutrophils. Both types of mycobacteria were internalized into phagosomes. However, whereas the LAMs of nonpathogenic mycobacteria resulted in the colocalization of LacCer with the Src family kinase Hck in the phagosomal membrane, the activation of Hck, and maturation of the phagosomes, the LAMs of pathogenic mycobacteria failed to induce LacCer-Hck clustering, thus preventing phagolysosome formation. These data suggest that targeting the LAMs of pathogenic mycobacteria may enhance the innate immune response to these pathogens, which could be beneficial in treating tuberculosis.

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