Evasion of Autophagy and Intracellular Killing by Human Myeloid Dendritic Cells Involves DC-SIGN-TLR2 Crosstalk

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Among the most successful of human microbes are intracellular pathogens. By entering the intracellular milieu, these pathogens are protected from harsh environmental factors in the host, including the humoral and cellular immune responses. Porphyromonas gingivalis is an opportunistic pathogen that colonizes the oral mucosa and accesses the bloodstream and distant sites such as the blood vessel walls, brain, placenta and other organs. Still unclear is how P. gingivalis traverses from oral mucosa to these distant sites. Dendritic cells are highly migratory antigen presenting cells that “patrol” the blood, skin, mucosa and all the major organ systems. Capture of microbes by dendritic cells activates a tightly regulated series of events, including directed migration towards the secondary lymphoid organs, where processed antigens are ostensibly presented to T cells. Autophagy is now recognized as an integral component of microbial clearance, antigen processing and presentation by dendritic cells. We report here that P. gingivalis is able to subvert autophagic destruction within dendritic cells. This occurs through its glycoprotein fimbriae, called Mfa-1, which targets the C-type lectin DC-SIGN on dendritic cells. The other major fimbriae on P. gingivalis, FimA, targets TLR2, which promotes autophagic destruction of P. gingivalis. We conclude that DC-SIGN-TLR2 crosstalk determines the intracellular fate of this pathogen within dendritic cells, and may have profound implications for the treatment of many chronic diseases involving low-grade infections.

Vyšlo v časopise: Evasion of Autophagy and Intracellular Killing by Human Myeloid Dendritic Cells Involves DC-SIGN-TLR2 Crosstalk. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004647
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004647

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