Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting dendritic cells in vitro with diverse th cell-polarizing signals.
Upon microbial infection, specific Th1 or Th2 responses develop depending on the type of microbe. Here, we demonstrate that different microbial compounds polarize the maturation of human myeloid dendritic cells (DCs) into stably committed Th1 cell-promoting (DC1) or Th2 cell-promoting (DC2) effector DCs that polarize Th cells via different mechanisms. Protein extract derived from the helminth Schistosoma mansoni induced the development of DC2s that promote the development of Th2 cells via the enhanced expression of OX40 ligand. Likewise, toxin from the extracellular bacterium Vibrio cholerae induced development of DC2s as well, however, via an OX40 ligand-independent, still unknown mechanism. In contrast, toxin from the intracellular bacterium Bordetella pertussis induced the development of DC1s with enhanced IL-12 production, which promotes a Th1 cell development. Poly(I:C) (dsRNA, mimic for virus) induced the development of extremely potent Th1-inducing DC1, surprisingly, without an enhanced IL-12 production. The obtained DC1s and DC2s are genuine effector cells that stably express Th cell-polarizing factors and are unresponsive to further modulation. The data suggest that the molecular basis of Th1/Th2 polarization via DCs is unexpectedly diverse and is adapted to the nature of the microbial compounds.
de Jong
Esther C
EC
Department of Cell Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. E.C.deJong@AMC.UvA.NL
Vieira
Pedro L
PL
Kalinski
Pawel
P
Schuitemaker
Joost H N
JH
Tanaka
Yuetsu
Y
Wierenga
Eddy A
EA
Yazdanbakhsh
Maria
M
Kapsenberg
Martien L
ML
D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D053278:OX40 Ligand; D011070:Poly I-C / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000947:Antigens, Helminth; D017077:Culture Media, Conditioned; D016207:Cytokines; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D010566:Virulence Factors, Bordetella; D018664:Interleukin-12; D002772:Cholera Toxin; D011070:Poly I-C