Human Dendritic Cells Respond to Helicobacter pylori, Promoting NK Cell and Th1-Effector Responses In Vitro

Autor: Markus Gerhard, Roland Rad, Petra Voland, S. Schwendy, Nadia Hafsi, Wolfgang Reindl, Christian Prinz
Rok vydání: 2004
Předmět:
Zdroj: The Journal of Immunology. 173:1249-1257
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.173.2.1249
Popis: Helicobacter pylori infection leads to chronic gastric inflammation. The current study determined the response of human APCs, NK cells, and T cells toward the bacteria in vitro. Human monocyte-derived dendritic cells (DC) were incubated with bacteria for 48 h. Intact H. pylori at a multitude of infection 5 stimulated the expression of MHC class II (4- to 7-fold), CD80, and CD86 B7 molecules (10- to 12-fold) and the CD83 costimulatory molecule (>30-fold) as well as IL-12 secretion (>50-fold) in DCs, and thereby, strongly induced their maturation and activation. CD56+/CD4− NK cells, as well as CD4+/CD45RA+ naive T cells, were isolated and incubated with DCs pulsed with intact bacteria or different cellular fractions. Coculture of H. pylori-pulsed DCs with NK cells strongly potentiated the secretion of TNF-α and IFN-γ. Coculture of naive T cells with H. pylori-pulsed DCs significantly enhanced TNF-α, IFN-γ, and IL-2 secretion as well as T-bet mRNA levels, while GATA-3 mRNA was lowered. However, the effect appeared attenuated compared with coculture with Escherichia coli. A greater stimulation was seen with naive T cells and DCs pulsed with H. pylori membrane preparations. Intact H. pylori potently induced the maturation and activation of human monocyte-derived DC and thereby promote NK and Th1 effector responses. The strong activation of NK cells may be important for the innate immune response. Th1-polarized T cells were induced especially by incubation with membrane preparations of H. pylori, suggesting that membrane proteins may account for the specific adaptive immune response.
Databáze: OpenAIRE