IFNγ enhances IL‐23 production during <i>Francisella</i> infection of human monocytes

Butchar, Jonathan P.; Parsa, Kishore V. L.; Marsh, Clay B.; Tridandapani, Susheela

doi:10.1016/j.febslet.2008.02.058

Cited by 12 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with our observations, IFN-γ was recently reported to enhance Francisella tularensis induced IL-23 in human monocytes [24]. IFN-γ allows for the transcription of IL-12p35 in response to LPS [25] and for the induction of IL-12 in response to a PAMP an additional stimulus such as IFN-γ is needed [5].…”

Section: Discussionsupporting

confidence: 86%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 86%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This result is in favor of the hypothesis that engagement to IL-23 production may persist in proinflammatory conditions such as natural killer cell activation (Butchar et al, 2007;Kim et al, 2009) or even after the DC-T cell interaction, leading to IFN-g production in the microenvironment. Moreover, IFN-g-priming of human monocytes or human monocytederived macrophages/DCs enhances IL-23 production during Francisella infection (Butchar et al, 2008) lipopolysaccharide treatment, respectively (Roses et al, 2008;Verreck et al, 2004). Interestingly, this increase in IL-23 production in NiSO 4 and IFN-g-activated MoDCs was accompanied with a higher fold induction of IL-12p70 as shown in this study and previously described by Antonios et al (2010), suggesting that IL-12p70 was the master regulatory cytokine in shaping T-cell responses in the case of DCs treated concomitantly with NiSO 4 and IFN-g.…”

Section: Discussionmentioning

confidence: 99%

Nickel Sulfate Promotes IL-17A Producing CD4+ T Cells by an IL-23-Dependent Mechanism Regulated by TLR4 and Jak-STAT Pathways

Bechara

Antonios

Azouri

et al. 2017

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction, and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. Whereas IL-12p70 promotes T helper (Th) 1 cell polarization, IL-23 promotes Th17 cell development and both have been isolated from nickel-allergic patients. In this work, we were interested in understanding the mechanism behind nickel-induced Th17 cell development. We showed that nickel induced an early production of IL-23 in human monocyte-derived dendritic cells along with an increase in the expression of il-23p19 and il-12p40 mRNA. However, the production of a significant level of IL-12p70 required an additional signal such as IFN-γ. Moreover, nickel-treated monocyte-derived dendritic cells induced an increase in the percentage of IL-17A CD4 T cells, an effect reduced by IL-23 neutralization. We then investigated the molecular mechanism of IL-23 production. Our results showed that toll-like receptor 4, p38 mitogen-activated protein kinase, and NF-κB were involved in IL-23 production induced by nickel. However, Jak-signal transducer and activator of transcription activation seems to maintain the IL-23/IL-12p70 balance by limiting IL-23 production and promoting Th1 polarization. These results indicate that nickel-induced Th17 cell development is dependent on the production of IL-23 by human monocyte-derived dendritic cells via toll-like receptor 4, p38 mitogen-activated protein kinase, NF-κB, and Jak-signal transducer and activator of transcription pathways.

show abstract

“…IFN-␥ is important in the activation of macrophages to effectively kill intracellular bacteria and in the induction of CD4 ϩ Th1 and CD8 ϩ cytotoxic T cell responses. IFN-␥ has been demonstrated to suppress Francisella replication inside macrophages, inhibit phagosome escape, and also induce the expression of IL-23 (3,5). Conversely, Francisella infection may suppress activation of STAT1 expression and phosphorylation, possibly through upregulated expression of suppressors of cytokine signaling 3 (SOCS3) (27).…”

Section: Discussionmentioning

confidence: 99%

Role of Francisella Lipid A Phosphate Modification in Virulence and Long-Term Protective Immune Responses

Kanistanon

Powell

Hajjar³

et al. 2012

Infect Immun

View full text Add to dashboard Cite

Lipopolysaccharide (LPS) structural modifications have been shown to specifically affect the pathogenesis of many Gramnegative pathogens. In Francisella, modification of the lipid A component of LPS resulted in a molecule with no to low endotoxic activity. The role of the terminal lipid A phosphates in host recognition and pathogenesis was determined using a Francisella novicida mutant that lacked the 4= phosphatase enzyme (LpxF). The lipid A of this strain retained the phosphate moiety at the 4= position and the N-linked fatty acid at the 3= position on the diglucosamine backbone. Studies were undertaken to determine the pathogenesis of this mutant strain via the pulmonary and subcutaneous routes of infection. Mice infected with the lpxF-null F. novicida mutant by either route survived primary infection and subsequently developed protective immunity against a lethal wild-type (WT) F. novicida challenge. To determine the mechanism(s) by which the host controlled primary infection by the lpxF-null mutant, the role of innate immune components, including Toll-like receptor 2 (TLR2), TLR4, caspase-1, MyD88, alpha interferon (IFN-␣), and gamma interferon(IFN-␥), was examined using knockout mice. Interestingly, only the IFN-␥ knockout mice succumbed to a primary lpxF-null F. novicida mutant infection, highlighting the importance of IFN-␥ production. To determine the role of components of the host adaptive immune system that elicit the long-term protective immune response, Tand B-cell deficient RAG1 ؊/؊ mice were examined. All mice survived primary infection; however, RAG1 ؊/؊ mice did not survive WT challenge, highlighting a role for T and B cells in the protective immune response.

show abstract

IFNγ enhances IL‐23 production during Francisella infection of human monocytes

Cited by 12 publications

References 22 publications

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

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

Nickel Sulfate Promotes IL-17A Producing CD4+ T Cells by an IL-23-Dependent Mechanism Regulated by TLR4 and Jak-STAT Pathways

Role of Francisella Lipid A Phosphate Modification in Virulence and Long-Term Protective Immune Responses

Contact Info

Product

Resources

About