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- Title
Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites.
- Authors
Lai Guan Ng; Hsu, Alice; Mandell, Michael A.; Roediger, Ben; Hoeller, Christoph; Mrass, Paulus; Iparraguirre, Amaya; Cavanagh, Lois L.; Triccas, James A.; Beverley, Stephen M.; Scott, Phillip; Weninger, Wolfgang
- Abstract
Dendritic cells (DC), including those of the skin, act as sentinels for intruding microorganisms. In the epidermis, DC (termed Langerhans cells, LC) are sessile and screen their microenvironment through occasional movements of their dendrites. The spatio-temporal orchestration of antigen encounter by dermal DC (DDC) is not known. Since these cells are thought to be instrumental in the initiation of immune responses during infection, we investigated their behavior directly within their natural microenvironment using intravital two-photon microscopy. Surprisingly, we found that, under homeostatic conditions, DDC were highly motile, continuously crawling through the interstitial space in a Gαi protein-coupled receptor-dependent manner. However, within minutes after intradermal delivery of the protozoan parasite Leishmania major, DDC became immobile and incorporated multiple parasites into cytosolic vacuoles. Parasite uptake occurred through the extension of long, highly dynamic pseudopods capable of tracking and engulfing parasites. This was then followed by rapid dendrite retraction towards the cell body. DDC were proficient at discriminating between parasites and inert particles, and parasite uptake was independent of the presence of neutrophils. Together, our study has visualized the dynamics and microenvironmental context of parasite encounter by an innate immune cell subset during the initiation of the immune response. Our results uncover a unique migratory tissue surveillance program of DDC that ensures the rapid detection of pathogens.
- Subjects
IMMUNE recognition; DENDRITIC cells; LANGERHANS cells; CELL motility; LEISHMANIA; NEUTROPHIL immunology; PROTOZOAN diseases
- Publication
PLoS Pathogens, 2008, Vol 4, Issue 11, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1000222