Unconventional maturation of dendritic cells induced by particles from the laminated layer of larval Echinococcus granulosus.
The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by the growth in internal organ parenchymae of fluid-filled structures (hydatids) that elicit surprisingly little inflammation in spite of their massive size and persistence. Hydatids are protected by a millimeter-thick layer of mucin-based extracellular matrix, termed the laminated layer (LL), which is thought to be a major factor determining the host response to the infection. Host cells can interact both with the LL surface and with materials that are shed from it to allow parasite growth. In this work, we analyzed the response of dendritic cells (DCs) to microscopic pieces of the native mucin-based gel of the LL (pLL). In vitro, this material induced an unusual activation state characterized by upregulation of CD86 without concomitant upregulation of CD40 or secretion of cytokines (interleukin 12 [IL-12], IL-10, tumor necrosis factor alpha [TNF-α], and IL-6). When added to Toll-like receptor (TLR) agonists, pLL-potentiated CD86 upregulation and IL-10 secretion while inhibiting CD40 upregulation and IL-12 secretion. In vivo, pLL also caused upregulation of CD86 and inhibited CD40 upregulation in DCs. Contrary to expectations, oxidation of the mucin glycans in pLL with periodate did not abrogate the effects on cells. Reduction of disulfide bonds, which are known to be important for LL structure, strongly diminished the impact of pLL on DCs without altering the particulate nature of the material. In summary, DCs respond to the LL mucin meshwork with a "semimature" activation phenotype, both in vitro and in vivo.
Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Cecilia
C
Casaravilla
Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Alvaro
A
Pittini
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Dominik
D
Rückerl
Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Paula I
PI
Seoane
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Stephen J
SJ
Jenkins
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Andrew S
AS
MacDonald
Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Ana M
AM
Ferreira
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Judith E
JE
Allen
Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) e Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay adiaz@fq.edu.uy.
Alvaro
A
Díaz
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D051940:B7-2 Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D048209:Echinococcus granulosus / Q000276:immunology*; D005260:Female; D006801:Humans; D007814:Larva / Q000276:immunology; D008810:Mice, Inbred C57BL
D000947:Antigens, Helminth; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines