Salmonella Induced IL-23 and IL-1β Allow for IL-12 Production by Monocytes and Mφ1 through Induction of IFN-γ in CD56+ NK/NK-Like T Cells

Diederik Van De Wetering,Roelof A De Paus,Jaap T Van Dissel,Esther Van De Vosse,Jacques Zimmer

doi:10.1371/journal.pone.0008396

Diederik Van De Wetering, Roelof A De Paus + Show 3 more

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https://doi.org/10.1371/journal.pone.0008396

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Journal: PloS one	Publication Date: Dec 21, 2009
Citations: 68	License type: CC BY 4.0

Affiliation: Leiden University Medical Center

Abstract

BackgroundThe type-1 cytokine pathway plays a pivotal role in immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the production of cytokines that activate lymphocytes to produce interferon (IFN)-γ. Interleukin (IL)-12 and IL-23 are thought to be the key cytokines required for initiating a type-1 cytokine immune response to Mycobacteria and Salmonellae. The relative contribution of IL-23 and IL-12 to this process is uncertain.Methodology/Principal FindingsWe show that various TLR agonists induce the production of IL-23 but not IL-12 in freshly isolated human monocytes and cultured human macrophages. In addition, type 1 pro-inflammatory macrophages (Mϕ1) differentiated in the presence of GM-CSF and infected with live Salmonella produce IL-23, IL-1β and IL-18, but not IL-12. Supernatants of Salmonella-infected Mϕ1 contained more IL-18 and IL-1β as compared with supernatants of Mϕ1 stimulated with isolated TLR agonists, and induced IFN-γ production in human CD56+ cells in an IL-23 and IL-1β-dependent but IL-12-independent manner. In addition, IL-23 together with IL-18 or IL-1β led to the production of GM-CSF in CD56+ cells. Both IFN-γ and GM-CSF enhanced IL-23 production by monocytes in response to TLR agonists, as well as induced IL-12 production.Conclusions/SignificanceThe findings implicate a positive feedback loop in which IL-23 can enhance its release via induction of IFN-γ and GM-CSF. The IL-23 induced cytokines allow for the subsequent production of IL-12 and amplify the IFN-γ production in the type-1 cytokine pathway.

Highlights

Immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria depends on the type-1 cytokine pathway [1]
To determine whether various Toll-like receptors (TLRs) agonists are capable of inducing IL-23 or IL-12 production in monocytes and MQ1, we first tested these capacities in freshly isolated human monocytes
The amounts of IL-23 produced by CD14+ monocytes varied somewhat between different donors, the relative amount released upon the various TLR stimulations was similar

Summary

Introduction

Immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria depends on the type-1 cytokine pathway [1]. This pathway is initiated by bacterial stimulation of pattern recognition receptors on monocytes and macrophages, resulting in the production of cytokines that activate lymphocytes and induce IFN-c production. The type-1 cytokine pathway critically depends on the crosstalk between monocytes/macrophages and lymphocytes. The type-1 cytokine pathway plays a pivotal role in immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the production of cytokines that activate lymphocytes to produce interferon (IFN)-c. The relative contribution of IL-23 and IL-12 to this process is uncertain

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Conclusion