The role of interleukin-12, and tissue antioxidants in chronic sinusitis

ABSTRACT Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

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Interleukin-12: Role of Interferon-γ in IL-12 Adverse Effects

Clinical Immunology and Immunopathology ◽

10.1006/clin.1996.4306 ◽

1997 ◽

Vol 83 (1) ◽

pp. 18-20 ◽

Cited By ~ 40

Author(s):

Bernhard Ryffel

Keyword(s):

Adverse Effects ◽

Interferon Γ ◽

Interleukin 12

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Resistance to Acute Babesiosis Is Associated with Interleukin-12- and Gamma Interferon-Mediated Responses and Requires Macrophages and Natural Killer Cells

Infection and Immunity ◽

10.1128/iai.71.4.2002-2008.2003 ◽

2003 ◽

Vol 71 (4) ◽

pp. 2002-2008 ◽

Cited By ~ 43

Author(s):

Irma Aguilar-Delfin ◽

Peter J. Wettstein ◽

David H. Persing

Keyword(s):

Nk Cells ◽

Gamma Interferon ◽

Interleukin 12 ◽

No Production ◽

Cytokine Responses ◽

Early Production ◽

Ifn Γ ◽

Crucial Part

ABSTRACT We examined the role of the cytokines gamma interferon (IFN-γ) and interleukin-12 (IL-12) in the model of acute babesiosis with the WA1 Babesia. Mice genetically deficient in IFN-γ-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WA1 Babesia, and observations were made on the course of infection and cytokine responses. Levels of IFN-γ and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-γ-mediated responses are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4+ T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4+ T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic Babesia WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-γ, and induction of macrophage-derived effector molecules like NO.

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Intranasal Interleukin-12 Treatment for Protection against Respiratory Infection with the Francisella tularensis Live Vaccine Strain

Infection and Immunity ◽

10.1128/iai.73.4.2306-2311.2005 ◽

2005 ◽

Vol 73 (4) ◽

pp. 2306-2311 ◽

Cited By ~ 67

Author(s):

Nathalie S. Duckett ◽

Sofia Olmos ◽

Douglas M. Durrant ◽

Dennis W. Metzger

Keyword(s):

Respiratory Infection ◽

Francisella Tularensis ◽

Vaccine Strain ◽

Live Vaccine ◽

Interleukin 12 ◽

Live Vaccine Strain ◽

Wild Type ◽

Intranasal Infection ◽

Ifn Γ

ABSTRACT Francisella tularensis is a gram-negative intracellular bacterium that can induce lethal respiratory infection in humans and rodents. However, little is known about the role of innate or adaptive immunity in protection from respiratory tularemia. In the present study, the role of interleukin-12 (IL-12) in inducing protective immunity in the lungs against intranasal infection of mice with the live vaccine strain (LVS) of F. tularensis was investigated. It was found that gamma interferon (IFN-γ) and IL-12 were strictly required for protection, since mice deficient in IFN-γ, IL-12 p35, or IL-12 p40 all succumbed to LVS doses that were sublethal for wild-type mice. Furthermore, exogenous IL-12 treatment 24 h before intranasal infection with a lethal dose of LVS (10,000 CFU) significantly decreased bacterial loads in the lungs, livers, and spleens of wild-type BALB/c and C57BL/6 mice and allowed the animals to survive infection; such protection was not observed in IFN-γ-deficient mice. The resistance induced by IL-12 to LVS infection was still observed in NK cell-deficient beige mice but not in CD8−/− mice. These results demonstrate that exogenous IL-12 delivered intranasally can prevent respiratory tularemia through a mechanism that is at least partially dependent upon the expression of IFN-γ and CD8 T cells.

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Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner

Infection and Immunity ◽

10.1128/iai.00361-09 ◽

2009 ◽

Vol 77 (9) ◽

pp. 3686-3695 ◽

Cited By ~ 30

Author(s):

Hany M. Ibrahim ◽

Hiroshi Bannai ◽

Xuenan Xuan ◽

Yoshifumi Nishikawa

Keyword(s):

Nitric Oxide ◽

Toxoplasma Gondii ◽

Inflammatory Responses ◽

Interleukin 12 ◽

Dependent Manner ◽

Independent Manner ◽

Necrosis Factor Alpha ◽

Parasite Multiplication ◽

Factor Alpha

ABSTRACT Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide (NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.

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