The Combination of a Tumor Necrosis Factor Inhibitor and Antibiotic Alleviates Staphylococcal Arthritis and Sepsis in Mice

Fei, Ying; Wang, Wanzhong; Kwieciński, Jakub; Josefsson, Elisabet; Pullerits, Rille; Jonsson, Ing-Marie; Magnusson, Mattias; Jin, Tao

doi:10.1093/infdis/jir266

Cited by 76 publications

(74 citation statements)

References 35 publications

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“…Indeed, pathological features associated with LPS-induced sepsis and IA have in common macrophage-activating cytokines TNF, IL-1, IL-6, or MCP-1 (30). However, sepsis is known to result from endotoxemia, whereas rheumatoid arthritis is not triggered by LPS, and our model of IA included LPS stimulation where the lack of LITAF could account for the difference.…”

Section: Discussionmentioning

confidence: 99%

Whole-body deletion of LPS-induced TNF-α factor (LITAF) markedly improves experimental endotoxic shock and inflammatory arthritis

Merrill

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Constable

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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LPS-induced TNF-α factor (LITAF) mediates cytokine expression in response to endotoxin challenge. Previously, we reported that macrophage-specific LITAF-deficient (macLITAF −/− ) mice exposed to LPS have a delayed onset in the serum levels of proinflammatory cytokines and prolonged persistence of anti-inflammatory cytokines, but only partial protection from endotoxic shock. We postulated that greater protection might be achieved if LITAF were deleted from all LITAF-producing cells, including macrophages. Using a Cre-loxP system, we engineered a tamoxifen-induced recombination mouse [tamLITAF(i)] that resulted in whole-body LITAF deficiency. Our findings demonstrate that (i) tamLITAF(i) −/− mice are more resistant to systemic Escherichia coli LPS-induced lethality than our previous macLITAF −/− mice, providing evidence that LITAF-producing cells other than LysMCre-positive cells play an important role in mediating endotoxic shock; (ii) tamLITAF(i) −/− mice show a similar pattern of cytokine expression with decreased proinflammatory and prolonged anti-inflammatory mediators compared with WT mice; and (iii) tamLITAF(i) −/− mice, compared with WT mice, display a significant reduction in bone resorption and inflammation associated with a local chronic inflammatory disease-namely, collagen antibody-induced arthritis. Our findings offer a unique model to study the role of LITAF in systemic and chronic local inflammatory processes, and pave the way for anti-LITAF therapeutic approaches for the treatment of TNF-mediated inflammatory diseases.septic shock | multiplex

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Section: Discussionmentioning

confidence: 99%

Whole-body deletion of LPS-induced TNF-α factor (LITAF) markedly improves experimental endotoxic shock and inflammatory arthritis

Merrill

You

Constable

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…into the tail vein with the TSST-1-producing S. aureus LS-1 strain in 0.2 ml of PBS. The LS-1 strain was isolated from a spontaneously arthritic NZB/W mouse (32) and has been used previously to study staphylococcal sepsis in mice (33,34). In most experiments, a lethal dose of bacteria (1.5 ϫ 10 8 to 3 ϫ 10 8 CFU/mouse) was inoculated, while a lower dose of bacteria (4 ϫ 10 7 CFU/mouse) was inoculated in a limited number of experiments as indicated.…”

Section: Methodsmentioning

confidence: 99%

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

et al. 2013

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Natural killer T (NKT) lymphocytes are implicated in the early response to microbial infection. Further, sulfatide, a myelin selfglycosphingolipid, activates a type II NKT cell subset and can modulate disease in murine models. We examined the role of NKT cells and the effect of sulfatide treatment in a murine model of Staphylococcus aureus sepsis. The lack of CD1d-restricted NKT cells did not alter survival after a lethal inoculum of S. aureus. In contrast, sulfatide treatment significantly improved the survival rate of mice with S. aureus sepsis, accompanied by decreased levels of tumor necrosis factor alpha and interleukin-6 in the blood. The protective effect of sulfatide treatment depended on CD1d but not on type I NKT cells, suggesting that activation of type II NKT cells by sulfatide has beneficial effects on the outcome of S. aureus sepsis in this model.

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“…The ability of protein A to activate ADAM17 rapidly seems crucial in this process, since TNFR1 is already available at the cell surface and thus can be cleaved before TNF-␣ is induced. Whereas blockade of TNF-␣ using a neutralizing antibody given in combination with antibiotics 3 days after infection reduces staphylococcal arthritis and sepsis (48), early studies with experimental models using recombinant TNF-␣ have demonstrated that this cytokine contributes to the initial host defense against S. aureus (49). Moreover, it has also been reported that inhibition of endogenous TNF-␣ increases mortality during S. aureus infection (11,48), demonstrating the important role of this cytokine during the initial host response.…”

Section: Fig 7 Inflammatory Response Induced During Systemic S Aureumentioning

confidence: 99%

Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection

et al. 2013

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Staphylococcus aureus infections are an important public health concern due to their increasing incidence and high rates of mortality. The success of S. aureus as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-␣) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-␣ receptor 1 (TNFR1). In this study, we demonstrate that S. aureus, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-␣ in vitro and in vivo. The results obtained using a protein A-deficient mutant and tnfr1 ؊/؊ mice strongly suggest that the increased levels of soluble TNFR1 present during experimental S. aureus infection may neutralize circulating TNF-␣ and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.

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The Combination of a Tumor Necrosis Factor Inhibitor and Antibiotic Alleviates Staphylococcal Arthritis and Sepsis in Mice

Cited by 76 publications

References 35 publications

Whole-body deletion of LPS-induced TNF-α factor (LITAF) markedly improves experimental endotoxic shock and inflammatory arthritis

Whole-body deletion of LPS-induced TNF-α factor (LITAF) markedly improves experimental endotoxic shock and inflammatory arthritis

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection

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