Year-end Sale % OFF 
Abstract
Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication.
Highlights
Macrophages and dendritic cells (DCs) are the sentinels of the innate immune system
We found that L. pneumophila infection rapidly induced DCs to commit cell death through apoptosis
Rapid apoptosis was not observed after infection of macrophages, which are the phagocytic cells that support L. pneumophila replication in the lungs of infected animals
Summary
They are key in sensing infection and activating downstream antimicrobial responses [1,2] These professional phagocytes are activated following stimulation of patternrecognition receptors, such as transmembrane Toll-like receptors (TLRs) and cytoplasmic nucleotide-binding domain and leucinerich repeat containing receptors (NLRs) by pathogen-associated molecular patterns (PAMPs). Bacterial pathogens that are able to infect and establish residence within macrophages and DCs provide a unique challenge to the innate immune system, as many pathogens have evolved virulence factors that subvert the cellular processes of these cells. One such pathogen is Legionella pneumophila, the etiological agent of the severe pneumonia known as Legionnaires’ disease [8,9]. L. pneumophila mutants defective in the Dot/Icm system do not replicate intracellularly, as they are unable to modulate intracellular transport and occupy a more conventional phagosome that undergoes rapid endocytic maturation [19,30]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
