1887

Abstract

The success of depends on its ability to survive within host macrophages. Here, avoids the acidic, hydrolytically competent environment of the phagolysosome by arresting phagosome maturation. Having shown previously that a mutant deficient in lipoprotein signal peptidase (LspA) is strongly attenuated in a mouse model of infection, we now studied putative mechanisms involved in attenuation of the  : :  mutant at a cellular level. In this work we investigated the ability of the mutant to interfere with two host defence mechanisms, i.e. Toll-like receptor (TLR)2-dependent immune response and phagosome maturation. While mycobacterial lipoproteins have been reported to trigger a TLR2 signalling pathway critical for innate immune responses, we found that growth control of the  : :  mutant was independent of TLR2. In addition, the  : :  mutant arrested phagosome maturation to an extent similar to that of the wild-type, as measured by lysosomal-associated membrane protein 1 (LAMP1) co-localization and intraphagosomal pH. These observations demonstrate severe attenuation even in the presence of arrested phagosome maturation, and point to a role for the early phagosome in growth restriction of the mutant.

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2008-10-01
2019-11-18
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