Differential pattern recognition receptor expression but stereotyped responsiveness in rat spleen dendritic cell subsets.
Dendritic cells (DC) are a heterogeneous population of APC endowed with specific functions. The nature of the DC subset involved in the course of an immune response to a specific pathogen might be important for inducing the appropriate effectors. In addition, each DC subset might also exhibit intrinsic functional plasticity. In the rat, spleen DC can be separated into three morphological and phenotypical distinct subsets, namely CD4+, CD4-, and plasmacytoid DC (pDC), whose frequencies are strain dependent. We correlated the expression of TLR and nucleotide-binding oligomerization domain 2 (NOD2) in these DC subsets to their in vitro responsiveness to specific ligands. CD4- DC expressed high levels of TLR1, 2, 3, and 10 mRNA, low TLR4, 5, 6, 7, and 9, and very low, if any, TLR8. pDC had a restricted repertoire characterized by high TLR7 and 9. CD4+ DC expressed all TLR and 10-fold higher levels of NOD2 mRNA than CD4- and pDC. Upon stimulation by TLR and NOD2 ligands, each DC subset responded in quite a stereotyped fashion. TLR2/6, 3, 4, 5, 9, and NOD2 triggering induced CD4- DC to mature and produce high IL-12p40, low IL-10, and TNF-alpha. TLR7/8 and 9 triggering induced pDC to mature and produce copious amounts of IL-6, IL-12p40, and TNF-alpha and low IFN-alpha. CD4+ DC were very poor producers of inflammatory cytokines. This study suggests that the nature of spleen DC responses to pathogens is dependent on subset specific-stimulation rather than intrinsic plasticity.
Hubert
François-Xavier
FX
INSERM Unité 643, Institut de Transplantation et de Recherche en Transplantation (ITERT), Centre Hospitalo-Universitaire Nantes, Hotel Dieu, 30 boulevard Jean Monnet, 44093 Nantes Cedex 1, France.
Voisine
Cécile
C
Louvet
Cédric
C
Heslan
Jean-Marie
JM
Ouabed
Asmahan
A
Heslan
Michèle
M
Josien
Régis
R
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007958:Leukocyte Count; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D053473:Nod2 Signaling Adaptor Protein; D021122:Protein Subunits / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C512493:NOD2 protein, rat; D053473:Nod2 Signaling Adaptor Protein; D021122:Protein Subunits; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12