Effects of endotoxin tolerance on Propionibacterium acnes-primed lipopolysaccharide hepatic injury

Margenthaler, Julie A.; Landeros, Keith; Kataoka, Makoto; Eilers, Mark; Ku, Grace; Flye, M. Wayne

doi:10.1016/s0022-4804(03)00133-1

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…The role of Th2-cytokines in the KRN7000-induced protection against disease is confirmed by experiments in which anti-IL-10 or anti-IL-4-neutralizing mAbs reverted protective effects by NKT ligand. These data are in agreement with previous findings [28,29] demonstrating that endotoxin tolerance and subsequent survival were associated with an increase of IL-4 and IL-10 release.…”

Section: Discussionsupporting

confidence: 94%

Pivotal Advance: α-Galactosylceramide induces protection against lipopolysaccharide-induced shock

Sireci

Manna

Sano

et al. 2006

Journal of Leukocyte Biology

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alpha-galactosylceramide, a natural killer T cell ligand, and its synthetic homolog, KRN7000, consistently influence IFN-gamma and TNF-alpha release, both mediators of LPS-induced shock. To modify the course of endotoxin shock, we injected KRN7000 at different time points of experimental systemic Shwartzman reaction. Mice treated with KRN7000 survived when it was injected within 2 h before and after LPS challenge. Mice survival was associated with low levels of T helper 1 (Th1) cytokines, such as IFN-gamma and TNF-alpha. By contrast, protection from endotoxin shock was associated with an increase of T helper 2 (Th2) cytokines, like IL-4 and IL-10. A role of Th2 cytokines in counteracting LPS-induced shock was supported by experiments in which the protection against Shwartzman reaction by KRN7000 was abrogated by in vivo coadministration of anti-Th2 cytokines antibodies. In addition, cytofluorimetric analysis showed that surviving animals have higher percentages of NKT-IL-10-positive cells and lower percentages of NKT-IFN-gamma and macrophages/TNF-alpha-stained cells than nonprotected mice. Taken together, our data demonstrate that KRN7000 treatment given at times near LPS challenge is protective for endotoxin shock inhibiting IFN-gamma and TNF-alpha release. Moreover, KRN7000-mediated protection occurs through an increased production of IL-4 and IL-10, which are mainly secreted by NKT cells. Since IFN-gamma release by NKT requires a longer TCR stimulation than that required for Th2 cytokines production, we demonstrate that timing of KRN7000 in vivo exposure affect the pattern of cytokines expression protecting animals by endotoxin shock.

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Section: Discussionsupporting

confidence: 94%

Pivotal Advance: α-Galactosylceramide induces protection against lipopolysaccharide-induced shock

Sireci

Manna

Sano

et al. 2006

Journal of Leukocyte Biology

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“…Furthermore, they exhibit enhanced susceptibility to the lethal effects of LPS and TNF-a (Galanos et al, 1988;Katschinski et al, 1992). In addition to LPS hypersensitivity, priming with P. acnes induces a number of other immunomodulatory effects, including inhibition of tumor growth (Fisher et al, 1975;Millman et al, 1977), intrahepatic granuloma formation, splenomegaly and extramedullary hematopoiesis (Adlam and Reid, 1977;Cummins and Linn, 1977;Halpern et al, 1964;Margenthaler et al, 2003;Riveros-Moreno and Niblock, 1979;Tsuji et al, 1999).…”

Section: Ifn-c-mediated Hypersensitivitymentioning

confidence: 99%

Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: Benefits and hazards of LPS hypersensitivity

et al. 2008

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“…Priming of mice with killed P. acnes represents a well-established experimental model that has been used to study these effects. P. acnes stimulates the reticuloendothelial system (6), whereby treated mice develop splenomegaly (7)(8)(9), extramedullary hemopoiesis, and intrahepatic granulomas (6,10). The degree of splenomegaly was shown to parallel the antitumor activity of P. acnes (11).…”

mentioning

confidence: 99%

Requirement for TLR9 in the Immunomodulatory Activity of Propionibacterium acnes

Kalis

Gumenscheimer

Freudenberg

et al. 2005

The Journal of Immunology

117

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Propionibacterium acnes (formerly Corynebacterium parvum) is part of the human flora and, as such, is associated with several human pathologies. It possesses strong immunomodulatory activities, which makes this bacterium interesting for prophylactic and therapeutic vaccination. The bacterial component(s) and the host receptor(s) involved in the induction of these activities are poorly understood. We show in this study that TLR9 is crucial in generating the characteristic effects of killed P. acnes priming in the spleen, such as extramedullary hemopoiesis and organ enlargement, and granuloma formation in the liver. Furthermore, the ability to overproduce TNF-α and IFN-γ in response to LPS, lipid A, synthetic lipopeptide Pam3CysK4, or whole killed bacteria was present in P. acnes-primed wild-type, but not TLR9−/−, mice. Finally, P. acnes priming failed to induce enhanced resistance to murine typhoid fever in TLR9−/− mice. Thus, TLR9 plays an essential role in the induction of immunomodulatory effects by P. acnes. Because IFN-γ is a key mediator of these effects, and enhanced IFN-γ mRNA expression was absent in spleen and liver of P. acnes-primed TLR9−/− mice, we conclude that TLR9 is required for the induction of IFN-γ by P. acnes.

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Effects of endotoxin tolerance on Propionibacterium acnes-primed lipopolysaccharide hepatic injury

Cited by 7 publications

References 32 publications

Pivotal Advance: α-Galactosylceramide induces protection against lipopolysaccharide-induced shock

Pivotal Advance: α-Galactosylceramide induces protection against lipopolysaccharide-induced shock

Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: Benefits and hazards of LPS hypersensitivity

Requirement for TLR9 in the Immunomodulatory Activity of Propionibacterium acnes

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