Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogens

Abstract

Summary Dendritic cells produce cytokines that regulate the class of the adaptive immune response. Microbial recognition is mediated, at least in part, by pattern recognition receptors such as Toll‐like receptors, which influence dendritic cell maturation. In humans it is not yet clear how intact pathogens modulate the developing immune response. To address the effects of intact pathogens on the maturation and effector functions of human dendritic cells, we investigated their responses to a number of microbial pathogens. We studied a range of micro‐organisms including Gram‐negative bacteria (Escherichia coli and Salmonella enterica sv. typhimurium), Gram‐positive cocci (Staphylococcus aureus) and atypical bacteria (Mycobacterium tuberculosis and Mycoplasma hominis) as well as the human protozoal parasite Trichomonas vaginalis. The micro‐organisms were fixed in formaldehyde to prevent replication whilst preserving surface morphology. All the pathogens induced similar up‐regulation of dendritic cell activation‐associated cell surface markers but there was a profound difference in the patterns of cytokines produced by the stimulated dendritic cells. Some pathogens (E. coli, Salmonella enterica sv. typhimurium and S. aureus) induced interleukin‐12 (IL‐12), IL‐10 and interferon‐α whereas others (M. tuberculosis, Mycoplasma hominis and T. vaginalis) induced only IL‐10. This differential effect was not altered by costimulation of the dendritic cells through CD40. These results support the notion that human dendritic cells are plastic in their response to microbial stimuli and that the nature of the pathogen dictates the response of the dendritic cell.

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

“…Consistent with this, our data showed that rshCD40L inhibited the growth of CD40 + pancreatic cancer cells (Pan-1, Aspc-1 and Miapaca-2) and induced apoptosis. Other studies also indicated that the role of CD40-CD40L in cancer immunity may involve activating DC to enhance the antigen-presenting, upregulating the expression of co-signaling molecules, and promoting the secretion of cytokines (29,33). However, the exact mechanisms of CD40-CD40L in pancreatic cancer remained to be clarified.…”

“…Unfortunately, the mechanism by which CD40-CD40L regulates immune functions is not fully known. There are reports indicating that CD40-CD40L suppressed cancer cell growth by promoting cell cycle arrest and/or apoptosis (28,29). In addition, studies have shown that expression of CD40 or its ligand on the surface of cancer cells increased the level of cellular adhesion molecule 1 (ICAM-1), unregulated Fas expression and sensitized the cancer cells to Fas-mediated apoptosis (30).…”

Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation

“…IL-12 and IL-10 are two cytokines, produced by DCs, involved in the regulation and balancing of the immune response, respectively, representing two important parameters to understand the type of immune response evoked [26]. We evaluated the percentage of IL-12 and IL-10 produced by MGL-engaged DCs by intracellular staining (Fig.…”

Inducing Immune Protection Against Trichomonas vaginalis: A Novel Vaccine Approach to Prevent HIV Transmission

“…Scott et al (2005) demonstrated that a symptomatic isolate of T. vaginalis induced only an IL-10 response in dendritic cells while a more diverse IL-12, IL-10 and IFN-repertoire was produced in response to selected infectious mucosal bacteria. Within the findings a potential relationship is noted between an IL-10 only response and chronicity of infection.…”