title: Migratory dermal dendritic cells act as rapid sensors of protozoan parasites.
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 Galpha(i) 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.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Alice
authors.initials: A
authors.lastname: Hsu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mandell
authors.forename: Ben
authors.initials: B
authors.lastname: Roediger
authors.forename: Christoph
authors.initials: C
authors.lastname: Hoeller
authors.forename: Paulus
authors.initials: P
authors.lastname: Mrass
authors.forename: Amaya
authors.initials: A
authors.lastname: Iparraguirre
authors.forename: Lois L
authors.initials: LL
authors.lastname: Cavanagh
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D056890:Eukaryota / Q000276:immunology*; D044385:GTP-Binding Protein alpha Subunits; D007113:Immunity, Innate; D018320:Leishmania major / Q000276:immunology; D008164:Luminescent Proteins; D051379:Mice; D008853:Microscopy; D010587:Phagocytosis; D011554:Pseudopodia / Q000276:immunology; D012867:Skin / Q000166:cytology*
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D008164:Luminescent Proteins