IL-12 and IFN-γ in host defense against mycobacteria and salmonella in mice and men

Jouanguy, Emmanuelle; Döffinger, Rainer; Dupuis, Stéphanie; Pallier, Annaïck; Altare, Frédéric; Casanova, Jean‐Laurent

doi:10.1016/s0952-7915(99)80055-7

Cited by 297 publications

(230 citation statements)

References 9 publications

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“…These results indicate a role for the level of Tlr4 expression in controlling the bacterial replication during the first 10 days of infection. However, in F1Tg388 mice, the spleen and liver bacterial load eventually increased during the late phase of infection to reach lethal numbers around days [15][16][17][18][19][20]. Therefore, the increased protection conferred by incremental Tlr4 expression appears to be limited to the early phase of infection suggesting that despite a robust innate immune response, the host is unable to mount protective adaptive immunity resulting in long-term control of the bacterial replication.…”

Section: Resultsmentioning

confidence: 99%

“…21,22 Administration of monoclonal antibodies directed against IL-12 exacerbates the mild disease caused by attenuated Salmonella 23 24 Moreover, the syndrome of Mendelian susceptibility to mycobacterial disease illustrates the importance of IL-12 and IFNg in the host response to Salmonella in humans. 18 Affected patients carrying a pathogenic mutation in one of the genes coding for the IFNg receptor, the IL-12 receptor or the IL-12 p40 subunit show increased susceptibility to environmental mycobacterial species and Salmonella. The IL-12/IFNg axis is therefore extremely important in immunity against Salmonella, most likely through its effect on the generation of a type 1 adaptive immune response.…”

Section: Discussionmentioning

confidence: 99%

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Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Larivière

Wilkinson

et al. 2006

Genes Immun

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Larivière

Wilkinson

et al. 2006

Genes Immun

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“…This exposure, however, does not affect mast cell activation through Fc⑀RI. Thus, IFN-␥ production associated with specific disease states, including bacterial or viral infections (27,50), provides a novel means by which the mast cell may be recruited into both immunologic and infectious diseases and may help explain the etiology of cellular reactions to Ag where Ag-specific IgE cannot be identified.…”

Section: Discussionmentioning

confidence: 99%

Expression of a Functional High-Affinity IgG Receptor, FcγRI, on Human Mast Cells: Up-Regulation by IFN-γ

Okayama

Kirshenbaum

Metcalfe

2000

The Journal of Immunology

170

152

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Biologically relevant activation of human mast cells through Fc receptors is believed to occur primarily through the high-affinity IgE receptor FcεRI. However, the demonstration in animal models that allergic reactions do not necessarily require Ag-specific IgE, nor the presence of a functional IgE receptor, and the clinical occurrence of some allergic reactions in situations where Ag-specific IgE appears to be lacking, led us to examine the hypothesis that human mast cells might express the high-affinity IgG receptor FcγRI and in turn be activated through aggregation of this receptor. We thus first determined by RT-PCR that resting human mast cells exhibit minimal message for FcγRI. We next found that IFN-γ up-regulated the expression of FcγRI. This was confirmed by flow cytometry, where FcγRI expression on human mast cells was increased from ∼2 to 44% by IFN-γ exposure. FcεRI, FcγRII, and FcγRIII expression was not affected. Scatchard plots were consisted with these data where the average binding sites for monomeric IgG1 (Ka = 4–5 × 108 M−1) increased from ∼2,400 to 12,100–17,300 per cell. Aggregation of FcγRI on human mast cells, and only after IFN-γ exposure, led to significant degranulation as evidenced by histamine release (24.5 ± 4.4%): and up-regulation of mRNA expression for specific cytokines including TNF-α, GM-CSF, IL-3 and IL-13. These findings thus suggest another mechanism by which human mast cells may be recruited into the inflammatory processes associated with some immunologic and infectious diseases.

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“…These cytokines or monokines activate innate immune effector cells, such as natural killer (NK) cells, to secrete interferon (IFN)-c and further drive pro-inflammatory cytokine production before the induction of adaptive immunity [7]. Early IFN-c production by NK cells is requisite for the further activation of monocytes and other innate immune cells to clear the host of invading pathogens, as evidenced by the susceptibility of mice lacking IFN-c to mycobacterial infections [8]. The importance of tight regulation in response to bacterial challenge is clear, as too little or too much monocyte/macrophage activation can result in death for the host [6].…”

Section: Introductionmentioning

confidence: 99%

STAT‐1‐mediated repression of monocyte interleukin‐10 gene expression in vivo

et al. 2006

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There have been substantial advances in understanding the events that regulate gene expression at the cellular and molecular level; however, there has been limited progress integrating this information to understand how biological systems function in vivo. For example, the anti‐inflammatory cytokine IL‐10 is thought to down‐regulate the effects of the pro‐inflammatory cytokine IFN‐γ on monocyte activation following LPS stimulation. However, the often‐postulated reciprocal regulation of IL‐10 gene expression by IFN‐γ has not been studied in vivo. Here we demonstrate that the regulation of IL‐10 gene expression has at least two phases following challenge with LPS or a gram‐negative organism. In C57BL/6 mice, early IL‐10 induction occurs independently of STAT‐1, while a delayed active repression of IL‐10 gene expression is critically dependent on STAT‐1, but only partially dependent upon IFN‐α/β and IFN‐γ. This in vivo IL‐10 production comes from blood monocytes, but not tissue macrophages, and cannot be reproduced in vitro. This study provides new insights into the regulation of IL‐10 following challenge with a gram‐negative organism, and highlights the importance of studying these cytokine regulatory pathways in vivo.

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IL-12 and IFN-γ in host defense against mycobacteria and salmonella in mice and men

Cited by 297 publications

References 9 publications

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

Expression of a Functional High-Affinity IgG Receptor, FcγRI, on Human Mast Cells: Up-Regulation by IFN-γ

STAT‐1‐mediated repression of monocyte interleukin‐10 gene expression in vivo

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