scholarly journals Immunostimulating Properties of Intragastrically Administered Acetobacter-Derived Soluble Branched (1,4)-β-d-Glucans Decrease Murine Susceptibility to Listeria monocytogenes

2004 ◽  
Vol 72 (12) ◽  
pp. 7005-7011 ◽  
Author(s):  
Wei Li ◽  
Toshiki Yajima ◽  
Kimika Saito ◽  
Hitoshi Nishimura ◽  
Takashi Fushimi ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Protective Immunity ◽  
Extracellular Polysaccharide ◽  
Interleukin 12 ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Strong Activity ◽  
Factor Alpha ◽  
Phosphate Buffered Saline

ABSTRACT We previously found that AC-1, an extracellular polysaccharide, produced by Acetobacter xylinum and composed of (1,4)-β-d-glucan with branches of glucosyl residues, showed a strong activity to induce production of interleukin-12 (IL-12) p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like receptor 4 (TLR-4) signaling. In the present study, we examined the effect of oral administration of AC-1 on protective immunity against Listeria monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS) intragastrically 2 days before, on the day of, and 2 days after an intraperitoneal inoculation of L. monocytogenes. The survival rate of AC-1-treated mice was significantly improved and bacterial growth in AC-1-treated mice was severely retarded compared to those of PBS-treated mice after infection with L. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+ Th1 and CD8+ Tc1 responses against Listeria antigen were significantly higher in AC-1-treated mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12 inducer through TLR-4, enhanced protective immunity against L. monocytogenes via augmentation of Th1 responses. These results suggest that infectious processes driven by intracellular microorganisms could be prevented to develop by the (1,4)-β-d-glucan.

scholarly journals Leishmania pifanoi Proteoglycolipid Complex P8 Induces Macrophage Cytokine Production through Toll-Like Receptor 4

2008 ◽  
Vol 76 (5) ◽  
pp. 2149-2156 ◽  
Author(s):  
Shanta M. Whitaker ◽  
Maria Colmenares ◽  
Karen Goldsmith Pestana ◽  
Diane McMahon-Pratt
Keyword(s):  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Cytokines And Chemokines ◽  
Inflammatory Protein ◽  
Tlr4 Ligand ◽  
Factor Alpha ◽  
Tlr4 Activation

ABSTRACT The P8 proteoglycolipid complex (P8 PGLC) is a glyconjugate expressed by Leishmania mexicana complex parasites. We previously have shown that vaccination with P8 PGLC provides protection against cutaneous leishmaniasis in susceptible BALB/c mice. However, the biological importance of this complex remains unknown. Here we show that P8 PGLC localizes to the surface of Leishmania pifanoi amastigotes and that upon exposure to macrophages, P8 PGLC binds and induces inflammatory cytokine and chemokine mRNAs such as tumor necrosis factor alpha and RANTES early after stimulation. Our studies indicate that cytokine and chemokine induction is dependent upon Toll-like receptor 4 (TLR4). Interestingly, key inflammatory cytokines and chemokines (such as interleukin-6 [IL-6], macrophage inflammatory protein 1β, and beta interferon [IFN-β]) that can be induced through TLR4 activation were not induced or only slightly upregulated by P8 PGLC. Activation by P8 PGLC does not occur in the presence of TLR4 alone and requires both CD14 and myeloid differentiation protein 2 for signaling; this requirement may be responsible for the limited TLR4 response. This is the first characterization of a TLR4 ligand for Leishmania. In vitro experiments indicate that L. pifanoi amastigotes induce lower levels of cytokines in macrophages in the absence of TLR4; however, notably higher IL-10/IFN-γ ratios were found for TLR4-deficient mice than for BALB/c mice. Further, increased levels of parasites persist in BALB/c mice deficient in TLR4. Taken together, these results suggest that TLR4 recognition of Leishmania pifanoi amastigotes is important for the control of infection and that this is mediated, in part, through the P8 PGLC.

scholarly journals Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of Genital Chlamydia muridarum Infection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production

2006 ◽  
Vol 75 (2) ◽  
pp. 666-676 ◽  
Author(s):  
Ashlesh K. Murthy ◽  
James P. Chambers ◽  
Patricia A. Meier ◽  
Guangming Zhong ◽  
Bernard P. Arulanandam
Keyword(s):  
Protective Immunity ◽  
Vaccination Strategy ◽  
Gamma Interferon ◽  
Productive Infection ◽  
Interleukin 12 ◽  
Bacterial Disease ◽  
Chlamydia Muridarum ◽  
Ifn Γ ◽  
Phosphate Buffered Saline

ABSTRACT There is currently no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Conventional vaccination attempts using surface-exposed chlamydial antigens have achieved only partial success. We have employed a novel vaccination strategy using a secreted protein, chlamydial protease-like activity factor (CPAF), which has been shown to degrade host major histocompatibility complex transcription factors and keratin-8 and therefore may allow immune evasion and establishment of a productive infection. Intranasal immunization using recombinant CPAF (rCPAF) plus interleukin-12 (IL-12) (rCPAF+IL-12 immunization) was used to assess the protective immunity against genital Chlamydia muridarum infection in BALB/c mice. rCPAF+IL-12 immunization induced robust gamma interferon (IFN-γ) production and minimal IL-4 production by splenocytes upon in vitro recall with rCPAF. The total and immunoglobulin G2a (IgG2a) anti-rCPAF antibody levels in serum were significantly elevated after rCPAF+IL-12 vaccination, as were the total antibody, IgG2a, and IgA levels in bronchoalveolar lavage and vaginal fluids when the animals were compared to animals that received rCPAF alone. rCPAF+IL-12-vaccinated mice displayed significantly reduced bacterial shedding upon chlamydial challenge and accelerated resolution of infection compared to mock-immunized (phosphate-buffered saline) animals. Moreover, rCPAF+IL-12-immunized animals exhibited protection against pathological consequences of chlamydial infection, including the development of hydrosalpinx and oviduct dilatation. This vaccination regimen also reduced the development of fibrosis and the influx of neutrophils into the upper genital tract when the animals were compared to mock-immunized (phosphate-buffered saline) animals after bacterial challenge. rCPAF+IL-12-mediated resolution of the bacterial infection and protection against Chlamydia-induced inflammatory disease were highly dependent on endogenous IFN-γ production. Together, these results demonstrate that secreted chlamydial antigens may be novel vaccine candidates to induce protective immunity.

scholarly journals Interleukin-12 p40 Secretion by Cutaneous CD11c+ and F4/80+ Cells Is a Major Feature of the Innate Immune Response in Mice That Develop Th1-Mediated Protective Immunity to Schistosomamansoni

2003 ◽  
Vol 71 (6) ◽  
pp. 3563-3571 ◽  
Author(s):  
Karen G. Hogg ◽  
Supeecha Kumkate ◽  
Sonia Anderson ◽  
Adrian P. Mountford
Keyword(s):  
Protective Immunity ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Innate Immune Responses ◽  
Toll Like Receptor 4 ◽  
Inflammatory Protein ◽  
Antigen Presenting ◽  
Macrophage Inflammatory Protein ◽  
Large Granular Cells

ABSTRACT Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1α and interleukin-1β (IL-1β) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10−/− mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40+ cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia+, consistent with their being antigen-presenting cells. Labeling of IL-12+ cells for CD11c, CD205, CD8α, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c− F4/80+, suggesting that macrophages were an additional source of IL-12 in the skin.

scholarly journals Miltefosine Efficiently Eliminates Leishmania major Amastigotes from Infected Murine Dendritic Cells without Altering Their Immune Functions

2009 ◽  
Vol 54 (2) ◽  
pp. 652-659 ◽  
Author(s):  
Klaus Griewank ◽  
Caroline Gazeau ◽  
Andreas Eichhorn ◽  
Esther von Stebut
Keyword(s):  
Dendritic Cells ◽  
Leishmania Major ◽  
Interleukin 12 ◽  
Immune Functions ◽  
Necrosis Factor Alpha ◽  
Mhc Ii ◽  
Intracellular Parasites ◽  
Factor Alpha

ABSTRACT As a treatment for leishmaniasis, miltefosine exerts direct toxic effects on the parasites. Miltefosine also modulates immune cells such as macrophages, leading to parasite elimination via oxidative radicals. Dendritic cells (DC) are critical for initiation of protective immunity against Leishmania through induction of Th1 immunity via interleukin 12 (IL-12). Here, we investigated the effects of miltefosine on DC in Leishmania major infections. When cocultured with miltefosine for 4 days, the majority of in vitro-infected DC were free of parasites. Miltefosine treatment did not influence DC maturation (upregulation of major histocompatibility complex II [MHC II] or costimulatory molecules, e.g., CD40, CD54, and CD86) or significantly alter cytokine release (IL-12, tumor necrosis factor alpha [TNF-α], or IL-10). Further, miltefosine DC treatment did not alter antigen presentation, since unrestricted antigen-specific proliferation of CD4+ and CD8+ T cells was observed upon stimulation with miltefosine-treated, infected DC. In addition, miltefosine application in vivo did not lead to maturation/emigration of skin DC. DC NO− production, a mechanism used by phagocytes to rid themselves of intracellular parasites, was also unaltered upon miltefosine treatment. Our data confirm prior studies indicating that in contrast to, e.g., pentavalent antimonials, miltefosine functions independently of the immune system, mostly through direct toxicity against the Leishmania parasite.

scholarly journals Interleukin 12 in Part Regulates Gamma Interferon Release in Human Whole Blood Stimulated with Leptospira interrogans

2003 ◽  
Vol 10 (2) ◽  
pp. 332-335 ◽  
Author(s):  
Maaike de Fost ◽  
Rudy A. Hartskeerl ◽  
Martijn R. Groenendijk ◽  
Tom van der Poll
Keyword(s):  
Whole Blood ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Leptospira Interrogans ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Human Whole Blood ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT Heat-killed pathogenic Leptospira interrogans serovar rachmati induced the production of gamma interferon (IFN-γ) and the IFN-γ-inducing cytokines interleukin-12p40 (IL-12p40) and tumor necrosis factor alpha in human whole blood in vitro. The production of IFN-γ was largely dependent on IL-12. These data establish that pathogenic leptospires can stimulate the production of type I cytokines involved in cellular immunity.

scholarly journals Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Mycobacterium smegmatis-Induced Cytokine Production by Human Macrophages In Vitro

2001 ◽  
Vol 69 (3) ◽  
pp. 1433-1439 ◽  
Author(s):  
Frank A. Post ◽  
Claudia Manca ◽  
Olivier Neyrolles ◽  
Bernhard Ryffel ◽  
Douglas B. Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Cytokine Production ◽  
Human Monocyte ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Vaccination of mice with Mycobacterium vaccae orM. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis, expressed in M. vaccae or M. smegmatis (M. smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-α) (P < 0.01), interleukin-12 (IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05), compared to infection with M. smegmatis vector (M. smegV). Infection with M. smeg19kDa and with M. smegV had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected withM. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated (M. smeg19NOG), nonsecreted (M. smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced production of TNF-α or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-α and IL-12 production, possibly leading to reduced induction of T-cell activation.

scholarly journals Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha.

1995 ◽  
Vol 181 (5) ◽  
pp. 1615-1621 ◽  
Author(s):  
I E Flesch ◽  
J H Hess ◽  
S Huang ◽  
M Aguet ◽  
J Rothe ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Mycobacterial Infection ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Interleukin 12 (IL-12) produced by macrophages immediately after infection is considered essential for activation of a protective immune response against intracellular pathogens. In the murine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) model we assessed whether early IL-12 production by macrophages depends on other cytokines. In vitro, murine bone marrow-derived macrophages produced IL-12 after infection with viable M. bovis BCG or stimulation with LPS, however, priming with recombinant interferon gamma (rIFN-gamma) was necessary. In addition, IL-12 production by these macrophages was blocked by specific anti-tumor necrosis factor alpha (TNF-alpha) antiserum. Macrophages from gene deletion mutant mice lacking either the IFN-gamma receptor or the TNF receptor 1 (p55) failed to produce IL-12 in vitro after stimulation with rIFN-gamma and mycobacterial infection. In vivo, IL-12 production was induced in spleens of immunocompetent mice early during M. bovis BCG infection but not in those of mutant mice lacking the receptors for IFN-gamma or TNF. Our results show that IL-12 production by macrophages in response to mycobacterial infection depends on IFN-gamma and TNF. Hence, IL-12 is not the first cytokine produced in mycobacterial infections.

scholarly journals Antiviral Effect of Resveratrol in Piglets Infected with Virulent Pseudorabies Virus

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 457 ◽  
Author(s):  
Xinghong Zhao ◽  
Wenzhi Tong ◽  
Xu Song ◽  
Renyong Jia ◽  
Lixia Li ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Control Measure ◽  
Antiviral Effect ◽  
Economic Losses ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Viral Loads ◽  
Factor Alpha ◽  
Potent Inhibitory Activity

Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in devastating disease and economic losses worldwide. Nevertheless, there are currently no antiviral drugs available for PRV infection. Resveratrol (Res) was identified to exert its antiviral activity by inhibiting the PRV replication in preliminary investigations. In our previous study, we found that Res has anti-PRV activity in vitro. Here, we show that Res can effectively reduce the mortality and increase the growth performance of PRV-infected piglets. After Res treatment, the viral loads significantly (p < 0.001) decreased. Pathological symptoms, particularly inflammation in the brain caused by PRV infection, were significantly (p < 0.001) relieved by the effects of Res. In Res-treated groups, higher levels of cytokines in serum, including interferon gama, interleukin 12, tumor necrosis factor-alpha and interferon alpha were observed at 7 days post infection. These results indicated that Res possesses potent inhibitory activity against PRV-infection through inhibiting viral reproduction, alleviating PRV-induced inflammation and enhancing animal immunity, suggesting that Res is expected to be a new alternative control measure for PRV infection.

scholarly journals Mannoproteins from Cryptococcus neoformans Promote Dendritic Cell Maturation and Activation

2005 ◽  
Vol 73 (2) ◽  
pp. 820-827 ◽  
Author(s):  
Donatella Pietrella ◽  
Cristina Corbucci ◽  
Stefano Perito ◽  
Giovanni Bistoni ◽  
Anna Vecchiarelli
Keyword(s):  
Cryptococcus Neoformans ◽  
Nuclear Factor Κb ◽  
Dendritic Cell Maturation ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Histocompatibility Complex ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Mannose Receptors

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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