Early IL-2 Production by Mouse Dendritic Cells Is the Result of Microbial-Induced Priming

Abstract

Dendritic cells (DCs) are professional APCs able to initiate innate and adaptive immune responses against invading pathogens. Different properties such as the efficient Ag processing machinery, the high levels of expression of costimulatory molecules and peptide-MHC complexes, and the production of cytokines contribute in making DCs potent stimulators of naive T cell responses. Recently we have observed that DCs are able to produce IL-2 following bacterial stimulation, and we have demonstrated that this particular cytokine is a key molecule conferring to early bacterial activated DCs unique T cell priming capacity. In the present study we show that many different microbial stimuli, but not inflammatory cytokines, are able to stimulate DCs to produce IL-2, indicating that DCs can distinguish a cytokine-mediated inflammatory process from the actual presence of an infection. The capacity to produce IL-2 following a microbial stimuli encounter is a feature shared by diverse DC subtypes in vivo, such as CD8α+ and CD8α− splenic DCs and epidermal Langerhans cells. When early activated DCs interact with T cells, IL-2 produced by DCs is enriched at the site of cell-cell contact, confirming the importance of DCs-derived IL-2 in T cell activation.

CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell‐produced IL‐2

“…Differently from T reg, CD4 + CD25 -lymphocytes require IL-2 for amplification of Ag specific response but not for their homeostatic maintenance [20,28]. DC produce low level of IL-2 in response to bacteria stimuli [29] or CD40 triggering [12], which however is very active in the synapse like interaction between DC and T cell and sufficient for initial triggering [12]. We found that DC but not T reg are the source of IL-2 upon their mutual interaction, confirming that T reg, are unable to secrete IL-2 [22,30,31].…”

“…5A). Since DC are able to produce IL-2 in response to microbial stimuli and CD40 triggering [12], we investigated which cell type between DC and T reg is actually secreting IL-2 upon CD3 stimulation. DC and T reg were gated to CD11c and to both CD4 and CD25, respectively and IL-2 detected by flow cytometry using a secretion assay.…”

Syk‐dependent ERK activation regulates IL‐2 and IL‐10 production by DC stimulated with zymosan

“…We and others have previously found that zymosan induces high levels of IL-2 and IL-10 production by DC [20,21,31,[38][39][40]. Other reports have indicated that these cytokines are produced in response to stimulation with TLR agonists, in particular those selective for TLR2 [26-29, 38, 41].…”

A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana

“…DC play a critical role in the initiation of immunity as antigen-presenting cells and by producing soluble factors, chemokines and cytokines, a few hours after the encounter with microbial signals [8,9]. DC are thought to distinguish different pathogens through the recognition of pathogen-associated molecular patterns (PAMP) via the expression of pattern recognition receptors (PRR), such as the Toll-like receptor family, that decode the microbial surface molecules [10][11][12][13].…”