Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with helminth antigens have a 'limited maturation' phenotype

TY - JOUR

T1 - Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with helminth antigens have a 'limited maturation' phenotype

AU - Ferret-Bernard, Stephanie

AU - Curwen, Rachel Sally

AU - Mountford, Adrian Paul

PY - 2008/3

Y1 - 2008/3

N2 - Dendritic cells (DCs) are important in the initiation of primary immune responses against pathogens. To aid understanding of how DCs guide T helper (Th)2-type responses, we employed 2-DE in association with MS/MS to identify proteins which characterise pro-Th2 DCs (matured with zero-to-three hours released proteins (0-3hRP), released by Schistosoma mansoni cercariae) versus pro-Th1 DCs (matured with lipopolysaccharide, LPS) and immature DCs. Software analysis of average 2-DE gels (three replicates per DC type) showed many similarities in the pattern of spots between the three groups of DCs but also marked changes. The major and significant changes in protein expression mainly affected cytoskeletal proteins. Other differences included chaperone proteins and enzymes involved in protein folding, S100 calcium-binding proteins, peroxiredoxin 1, superoxide dismutase 1, several annexins and arginase 1. Our study demonstrates that pro-Th2 DCs matured with 0-3hRP exhibit a proteome that is intermediate between that of immature DCs and pro-Th1 DCs. Finally, the differential regulation of protein spots identified by MALDI-MS/MS as having cytoskeletal and morphological functions was confirmed by contrast, confocal and scanning electron microscopy examination of DCs. Together, our results support the view that Th2 differentiation results from a 'limited maturation' of DCs.

AB - Dendritic cells (DCs) are important in the initiation of primary immune responses against pathogens. To aid understanding of how DCs guide T helper (Th)2-type responses, we employed 2-DE in association with MS/MS to identify proteins which characterise pro-Th2 DCs (matured with zero-to-three hours released proteins (0-3hRP), released by Schistosoma mansoni cercariae) versus pro-Th1 DCs (matured with lipopolysaccharide, LPS) and immature DCs. Software analysis of average 2-DE gels (three replicates per DC type) showed many similarities in the pattern of spots between the three groups of DCs but also marked changes. The major and significant changes in protein expression mainly affected cytoskeletal proteins. Other differences included chaperone proteins and enzymes involved in protein folding, S100 calcium-binding proteins, peroxiredoxin 1, superoxide dismutase 1, several annexins and arginase 1. Our study demonstrates that pro-Th2 DCs matured with 0-3hRP exhibit a proteome that is intermediate between that of immature DCs and pro-Th1 DCs. Finally, the differential regulation of protein spots identified by MALDI-MS/MS as having cytoskeletal and morphological functions was confirmed by contrast, confocal and scanning electron microscopy examination of DCs. Together, our results support the view that Th2 differentiation results from a 'limited maturation' of DCs.

KW - cytoskeleton

KW - dendritic cell

KW - innate immune cell

KW - parasitic helminth

KW - Th2 lymphocyte

KW - ACTIVATED PROTEIN-KINASE

KW - SCHISTOSOMA-MANSONI

KW - IMMUNE-RESPONSES

KW - CYTOKINE PRODUCTION

KW - CUTTING EDGE

KW - EXPRESSION

KW - DIFFERENTIATION

KW - MACROPHAGES

KW - LARVAE

KW - IDENTIFICATION

UR - http://www.scopus.com/inward/record.url?scp=41149139805&partnerID=8YFLogxK

U2 - 10.1002/pmic.200700538

DO - 10.1002/pmic.200700538

M3 - Article

SN - 1615-9853

VL - 8

SP - 980

EP - 993

JO - Proteomics

JF - Proteomics

IS - 5

ER -