IL-12-Independent Th1<i>-</i>Type Immune Responses to Respiratory Viral Infection: Requirement of IL-18 for IFN-γ Release in the Lung But Not for the Differentiation of Viral-Reactive Th1<i>-</i>Type Lymphocytes

Xing, Zhou; Zganiacz, Anna; Jun, Wang; Divangahi, Maziar; Nawaz, Fauzia

doi:10.4049/jimmunol.164.5.2575

Cited by 64 publications

(68 citation statements)

References 30 publications

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“…32 IL-18 and/or IL-12 are candidates for such a factor because (1) both are released by AMs after exposure to adenovirus, (2) both strongly stimulate IFN-␥ production by T cells, and (3) blocking IL-18 and IL-12 signaling impairs IFN-␥ production following pulmonary adenovirus infection. 30 Together, these observations suggest that GM-CSF might regulate both Fc␥R-mediated phagocytosis by AMs and the IL-18/IFN-␥ pathway that is required for augmentation of AM Fc␥R expression following pulmonary infection. To address this hypothesis, the role of GM-CSF and PU.1 in Fc␥R-mediated phagocytosis was assessed in primary AMs from GM ϩ/ϩ , GM Ϫ/Ϫ , or SPC-GM ϩ/ϩ /GM Ϫ/Ϫ mice and in cultured AM cell lines from GM ϩ/ϩ and GM Ϫ/Ϫ mice.…”

Section: Introductionmentioning

confidence: 88%

“…Because IL-18 and IL-12 stimulate IFN-␥ production in the lung during pulmonary adenovirus infection, 30 these cytokines were also quantified after pulmonary adenoviral infection. Neither IL-18 nor IL-12 was detected in the lungs of uninfected mice (data not shown).…”

Section: Impairment Of Ifn-␥ Il-18 and Il-12 Expression In Gm ؊/؊ Mmentioning

confidence: 99%

“…27,28 Infection by microbial pathogens including adenovirus 29 stimulates IFN-␥ production by various cells, eg, natural killer (NK) and T helper-1 (T H1 ) cells. 30 IFN-␥ secretion by these cells is stimulated by either interleukin-18 (IL-18) or IL-12, both of which are released by AMs after exposure to pathogens such as adenovirus. 30 Thus, IL-18/IL-12-stimulated IFN-␥ secretion forms a feedback loop that enhances AM Fc␥R-mediated opsonophagocytosis during microbial lung infection.…”

Section: Introductionmentioning

confidence: 99%

“…30 IFN-␥ secretion by these cells is stimulated by either interleukin-18 (IL-18) or IL-12, both of which are released by AMs after exposure to pathogens such as adenovirus. 30 Thus, IL-18/IL-12-stimulated IFN-␥ secretion forms a feedback loop that enhances AM Fc␥R-mediated opsonophagocytosis during microbial lung infection. GM Ϫ/Ϫ mice have a blunted IFN-␥ response to in vivo lipopolysaccharide exposure although GM Ϫ/Ϫ T cells have a normal IFN-␥ response in vitro.…”

Section: Introductionmentioning

confidence: 99%

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GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

Berclaz

Shibata

Whitsett

et al. 2002

Blood

120

101

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Severely impaired pulmonary microbial clearance was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)–deficient mice. To determine mechanisms by which GM-CSF mediates lung host defense, FcγR-mediated phagocytosis (opsonophagocytosis) by alveolar macrophages (AMs) was assessed in GM-CSF–sufficient (GM+/+) and –deficient (GM−/−) mice and in GM−/− mice expressing GM-CSF only in the lungs from a surfactant protein C (SPC) promoter (SPC-GM+/+/GM−/−). Opsonophagocytosis by GM−/− AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Defective opsonophagocytosis by GM−/− AMs was associated with decreased FcγR expression. Because interferon-γ (IFN-γ) augments macrophage FcγR levels, the role of GM-CSF/PU.1 in the regulation of AM FcγR expression by IFN-γ was assessed during adenoviral lung infection. Adenoviral infection stimulated IFN-γ production and augmented FcγR levels on AMs in GM-CSF–expressing but not GM−/− mice. However, IFN-γ exposure ex vivo stimulated FcγR expression on GM−/− AMs. Because interleukin-18 (IL-18) and IL-12 stimulate IFN-γ production during adenoviral infection, their role in GM-CSF/PU.1 regulation of IFN-γ–augmented FcγR expression on AMs was assessed. Adenoviral infection stimulated IL-18 and IL-12 production in GM-CSF–expressing mice, but both were markedly reduced or absent in GM−/−mice. IL-18 expression by GM−/− AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Pulmonary administration of IL-18 in GM−/− mice stimulated IFN-γ production and restored FcγR expression on AMs. These results show that GM-CSF, via PU.1, regulates constitutive AM FcγR expression and opsonophagocytosis and is required for the IFN-γ–dependent regulation of AM FcγR expression, enabling AMs to release IL-18/IL-12 during lung infection.

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Section: Introductionmentioning

confidence: 88%

Section: Impairment Of Ifn-␥ Il-18 and Il-12 Expression In Gm ؊/؊ Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

Berclaz

Shibata

Whitsett

et al. 2002

Blood

120

101

View full text Add to dashboard Cite

show abstract

“…49 Ninety-six-well ELISA plates (Nalge Nunc International, Rochester, NY) were coated with 2.5 g per well of influenza-infected MDCK cell lysate and incubated at 4°C overnight. Wells were then blocked with Blocking buffer (1% bovine serum albumin in PBS) for 1 hour at 37°C.…”

Section: Influenza-specific Antibody Elisamentioning

confidence: 99%

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

Damjanovic

Divangahi

Kugathasan

et al. 2011

The American Journal of Pathology

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Lung immunopathology is the main cause of influenzamediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-␣ (TNF-␣) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-␣-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-␣ was up-regulated in the lung after influenza infection, it was not required for normal influenza viral clearance. However, TNF-␣ deficiency led not only to a greater extent of illness but also to heightened lung immunopathology and tissue remodeling. The severe lung immunopathology was associated with increased inflammatory cell infiltration, anti-influenza adaptive immune responses, and expression of cytokines such as monocyte chemoattractant protein-1 (MCP-1) and fibrotic growth factor, TGF-␤1. Thus, in vivo neutralization of MCP-1 markedly attenuated lung immunopathology and blunted TGF-␤1 production following influenza infection in these hosts. On the other hand, in vivo transgenic expression of MCP-1 worsened lung immunopathology following influenza infection in wild-type hosts. Thus, TNF-␣ is dispensable for influenza clearance; however, different from the traditional belief, this cytokine is critically required for negatively regulating the extent of lung immunopathology during acute influenza infection.

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Interleukin‐18 enhances HIV‐1 production in a human chronically‐infected T cell line (H9‐V)

Pugliese

Gennero

Vidotto

et al. 2002

Cell Biochemistry & Function

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Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine expressed by activated macrophages, that induces production of interferon-gamma (IFN-gamma) and Th-1 development. Recently some investigators reported controversial in vitro data on IL-18 stimulation of HIV-1 replication in several cell lines. In the present study the effect of IL-18 on HIV replication in a human chronically HIV-1-infected lymphocytic T cell line (H9-V) was investigated. HIV-1 replication was determined by an immunoassay method in order to evaluate the content of p24 antigen in the cell culture supernatants. Stimulation of H9-V cells with IL-18 resulted in increased production of p24, especially at concentrations of 0.01 microg ml(-1) and 0.10 microg ml(-1). Moreover a significant and persistent IL-18 stimulation of HIV-1 replication was observed at a concentration of 0.01 microg ml(-1) during a 7-day period. Pre-treatment of IL-18 with a specific neutralizing monoclonal antibody significantly reduced HIV-1 replication. These experiments show that IL-18 promotes the increase of HIV-1 replication in human chronically-infected lymphocytic T cells and confirm the role of IL-18 as a proimflammatory cytokine in stimulating and maintaining HIV-1 replication during the course of the disease. In a successive set of experiments, since one of the main activities of IL-18 is the induction of IFN-gamma, we evaluated the effect of this biological modifier on H9-V cells. In particular, IFN-gamma shows a significant effect on cell replication and on reduction of CD4 and CD71 surface expression.

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IL-12-Independent Th1-Type Immune Responses to Respiratory Viral Infection: Requirement of IL-18 for IFN-γ Release in the Lung But Not for the Differentiation of Viral-Reactive Th1-Type Lymphocytes

Cited by 64 publications

References 30 publications

GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

Interleukin‐18 enhances HIV‐1 production in a human chronically‐infected T cell line (H9‐V)

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