Interleukin-12 enhances murine survival against acute toxoplasmosis

Khan, Imtiaz Ali; Matsuura, Tadashi; Kasper, Lloyd H.

doi:10.1128/iai.62.5.1639-1642.1994

Cited by 183 publications

(77 citation statements)

References 17 publications

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“…9,28,67 IL-12 has a central role in protection of the host during parasitic infection with either T. gondii or L. donovani. 28,[67][68][69][70][71] In particular, the importance of progesterone as an exacerbatory factor during in vivo T. gondii infection may be a consequence of IL-12 inhibition and subsequent downregulation of the protective type-1 response. This may be a major factor in explaining why T. gondii is a common congenital infection.…”

Section: Discussionmentioning

confidence: 99%

Toll‐like receptor‐4‐mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors

et al. 2008

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Summary Macrophage function has been demonstrated to be subject to modulation by progesterone. However, as this steroid hormone can act through the glucocorticoid receptor as well as the progesterone receptor, the mechanism of action has not been precisely characterized. To determine the mode of action, we compared the ability of progesterone, norgestrel (a synthetic progesterone‐receptor‐specific agonist) and dexamethasone (a synthetic glucocorticoid receptor agonist) to modulate macrophage function following stimulation of the Toll‐like receptor‐4 (TLR‐4) ligand lipopolysaccharide (LPS). The results demonstrate that following stimulation of TLR‐4 with LPS and cotreatment with either progesterone or dexamethasone, but not norgestrel, there is a significant reduction in nitric oxide (NO) production, indicating that this progesterone‐mediated effect is through ligation of the glucocorticoid receptor. In contrast, LPS‐induced interleukin‐12 (IL‐12) production could be downregulated by all three steroids, indicating that ligation by progesterone of either the glucocorticoid or the progesterone receptors or both could mediate this effect. While progesterone downmodulated NO‐mediated killing of Leishmania donovani by activated macrophages in vitro, most probably via the glucocorticoid receptor, it had little effect on Toxoplasma gondii growth in these cells. This would suggest that progesterone‐mediated increased susceptibility to T. gondii during pregnancy is more likely to be related to the ability of the hormone to downregulate IL‐12 production and a type‐1 response utilizing the progesterone as well as the glucocorticoid receptors.

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Section: Discussionmentioning

confidence: 99%

Toll‐like receptor‐4‐mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors

et al. 2008

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“…IL-12 is also known to be an anti-tumour cytokine; it activates NK cells, conventional T cells [9][10][11][12]15,16] and T cells with NK cell markers [18,19,29,30,33,34] and endows potent antitumour activities to these cells in both human and mice. Another important function of IL-12 is its anti-parasitic effect; it is required for mouse resistance against Toxoplasma gondii and Leishmania major [35][36][37]. On the other hand, the role of IL-12 in viral infections is controversial; it aggravates viral infections in certain conditions [38].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD)

Takata

Seki²,

Dobashi

et al. 1998

Clinical and Experimental Immunology

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SUMMARYThe aim of this study was to further assess the role of pooled human immunoglobulin (PHIG) on cytokine production from PBMC stimulated with a bacterial superantigen. Human PBMC were cultured with Streptococcus pyrogenic exotoxin A (SPE-A) with or without PHIG and several proinflammatory cytokine levels of culture supernatants were measured. Serum cytokine levels of KD patients before and after PHIG therapy were also examined. PHIG greatly reduced the production of IL-12, interferongamma (IFN-g) and other cytokines from SPE-A-stimulated PBMC, while exogenous IL-12, but neither IL-1 nor tumour necrosis factor-alpha (TNF-a), restored IFN-g production inhibited by PHIG. Although PHIG partially adsorbed SPE-A, its inhibitory effect on cytokine production was not played by anti-SPE-A antibody. Although purified CD4þ T cells cultured with human HLA-DR-transfected mouse L cells and SPE-A could not effectively produce IFN-g, they produced large amounts of IFN-g if exogenous IL-12 was introduced. KD patients in the acute phase had higher levels of serum IFN-g than did controls and patients with bacterial infection. Although IL-12 levels of children with or without KD were not significantly different, IL-12 levels of children were much higher than those of adults. However, serum levels of IL-12 of KD patients were transiently but significantly decreased by PHIG therapy and IFN-g amounts subsequently reverted to basal levels thereafter. These findings indicate that PHIG inhibits IL-12 production of SPE-A-activated monocytes and thereby decreases IFN-g synthesis by T cells and suggest that inhibition of IL-12 and IFN-g production is an important part of the mechanisms underlying PHIG therapy on KD.

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“…Additionally, macrophage and natural killer cell interactions (14), CD4 ϩ Th1 cells (11), and antibody formation (10) are believed to contribute to resistance against toxoplasmosis. Many of these cells exert protective effects through the production of pro-inflammatory cytokines such as IL-1 (8), IL-2 (27), IL-12 (19), IFN-γ (28), and TNF-α (17). In contrast, Th2 cells and their cytokine productions down-regulate Th1 cell responses, interfering with Th1-produced cytokines and their effects (12).…”

mentioning

confidence: 99%

Induction of Protective Immunity by Primed B‐1 Cells in Toxoplasma gondii‐Infected B Cell‐Deficient Mice

Chen

Mun

et al. 2003

Microbiology and Immunology

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Abstract:We examined the role of B-1 cells in protection against Toxoplasma gondii infection using B celldeficient mice (MT mice). We found that primed but not naïve B-1 cells from wild-type C57BL/6 mice protected B cell-deficient recipients from challenge infection. All MT mice transferred with primed B-1 cells survived more than 5 months after T. gondii infection, whereas 100% of MT mice transferred with naïve B-1 cells succumbed by 18 days after infection. Additionally, high expression of both T help (Th) 1-and Th2-type cytokines and a high level of nitric oxide production were observed in T. gondii-infected MT mice transferred with primed B-1 cells. Thus, it was clearly demonstrated that B-1 cells play an important role in host protection against T. gondii infection in MT mice.

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Interleukin-12 enhances murine survival against acute toxoplasmosis

Cited by 183 publications

References 17 publications

Toll‐like receptor‐4‐mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors

Toll‐like receptor‐4‐mediated macrophage activation is differentially regulated by progesterone via the glucocorticoid and progesterone receptors

Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD)

Induction of Protective Immunity by Primed B‐1 Cells in Toxoplasma gondii‐Infected B Cell‐Deficient Mice

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