The role of interleukin-12 receptor aberrations in isolated immune deficits causing atypical mycobacterial infection in an otherwise normal host

2009 ◽  
Vol 60 (3) ◽  
pp. AB203
Keyword(s):  
Mycobacterial Infection ◽  
Interleukin 12 ◽  
Normal Host ◽  
Atypical Mycobacterial Infection

scholarly journals Role of Interleukin-18 (IL-18) in Mycobacterial Infection in IL-18-Gene-Disrupted Mice

1999 ◽  
Vol 67 (5) ◽  
pp. 2585-2589 ◽  
Author(s):  
Isamu Sugawara ◽  
Hiroyuki Yamada ◽  
Hirotaka Kaneko ◽  
Satoru Mizuno ◽  
Kiyoshi Takeda ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Mycobacterial Infection ◽  
Granuloma Formation ◽  
Interleukin 12 ◽  
No Production ◽  
Main Function ◽  
Wild Type ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-γ), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-α), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-γ, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-γ production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis andMycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-γ levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-γ production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-γ expression.

scholarly journals Acquired Resistance but Not Innate Resistance toMycobacterium bovis Bacillus Calmette-Guérin Is Compromised by Interleukin-12 Ablation

1998 ◽  
Vol 66 (11) ◽  
pp. 5268-5274 ◽  
Author(s):  
LuAnn Thompson-Snipes ◽  
Emil Skamene ◽  
Danuta Radzioch
Keyword(s):  
Immune Response ◽  
Acquired Resistance ◽  
Mycobacterial Infection ◽  
Effective Control ◽  
Interleukin 12 ◽  
Mrna Levels ◽  
Innate Resistance ◽  
Threefold Increase ◽  
Ifn Γ

ABSTRACT Interleukin-12 (IL-12) is one of the first cytokines produced by macrophages, key mediators of innate resistance, during the host’s immune response to infections. Therefore, in this study we propose that IL-12 has an important role in the early phase of the immune response to Mycobacterium bovis BCG. IL-12 has been shown to enhance the maturation of protective Th1 cells and gamma interferon (IFN-γ) production during mycobacterial infection. Therefore, it may play a crucial role during the immune phase of infection as well. To examine the role of IL-12 in both the innate and the immune phase of infection, we compared BCG-resistant mice, B10.A (Bcgr ), to the susceptible congenic strain B10.A (Bcgs ) following administration of a blocking monoclonal antibody to IL-12 (10F6). Anti-IL-12-treated susceptible animals exhibited a two- to threefold increase in spleen CFU by day 21. In contrast, anti-IL-12 treatment had little or no effect on the response of the genetically resistant animals to infection. The B10.A (Bcgr ) but not the B10.A (Bcgs ) mice had an increase in IFN-γ mRNA relative to baseline levels as early as day 1 of infection irrespective of anti-IL-12 treatment. By day 14, B10.A (Bcgr ) mice showed a decrease in IFN-γ mRNA while the B10.A (Bcgs ) mice showed a significant increase in IFN-γ mRNA levels. Thus, during BCG infection, the B10.A (Bcgr ) mice mount an early IFN-γ response against BCG whereas the B10.A (Bcgs ) mice have a delayed IFN-γ response correlating with their genetic permissiveness expressed as an increased mycobacterial load by day 21. Overall, our data demonstrate that the inherent resistance of B10.A (Bcgr ) mice to mycobacteria does not depend on optimal levels of IL-12 to maintain effective control of the bacteria, whereas IL-12 is important for the susceptible animals’ response to BCG during the peak of infection.

Paediatric neck abscesses: microbiology and management

2007 ◽  
Vol 122 (5) ◽  
pp. 480-484 ◽  
Author(s):  
I K Rustom ◽  
J A T Sandoe ◽  
Z G G Makura
Keyword(s):  
Mycobacterial Infection ◽  
Neck Mass ◽  
Atypical Mycobacteria ◽  
Incision And Drainage ◽  
Presenting Symptoms ◽  
General Infirmary ◽  
Intravenous Antibiotics ◽  
Atypical Mycobacterial Infection ◽  
The Mean

AbstractIntroduction:Paediatric neck abscesses remain common problems which are sometimes difficult to manage.Methods and materials:We conducted a retrospective study of 64 children who underwent incision and drainage of neck abscesses at Leeds General Infirmary from 1 February 2002 to 31 July 2006. The aim of this study was to identify the presenting symptoms in children, the appropriateness of prescribed antibiotics and the role of atypical mycobacteria in neck infections. The outcome measure was clinical resolution of the abscess.Results:The mean presenting age was 44.2 months (3.68 years). The commonest sign and symptom was neck mass (96.9 per cent). The mean period of hospitalisation was 3.7 (± standard deviation of 1.9) days. Staphylococcus aureus (48.4 per cent) was the commonest organism cultured. Atypical mycobacteria were found in only 4.7 per cent of the specimens. Flucloxacillin was the most common antibiotic used (57.8 per cent), often in combination with other antimicrobials. The abscess recurrence rate was 4.7 per cent. No fatalities occurred in this series of patients.Conclusion:Appropriately prescribed intravenous antibiotics and surgical drainage remain the central core of treatment. Atypical mycobacterial infection is an important differential diagnosis of a painless, cervico-facial mass. An algorithm for the management of paediatric neck abscesses is proposed.

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.

scholarly journals Protective role of membrane tumour necrosis factor in the host’s resistance to mycobacterial infection

Immunology ◽  
2008 ◽  
Vol 125 (4) ◽  
pp. 522-534 ◽  
Author(s):  
Nasiema Allie ◽  
Lena Alexopoulou ◽  
Valerie J. F. Quesniaux ◽  
Lizette Fick ◽  
Ksanthi Kranidioti ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Mycobacterial Infection ◽  
Protective Role ◽  
Necrosis Factor

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

2003 ◽  
Vol 71 (4) ◽  
pp. 2002-2008 ◽  
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.

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

2005 ◽  
Vol 73 (4) ◽  
pp. 2306-2311 ◽  
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.

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

2009 ◽  
Vol 77 (9) ◽  
pp. 3686-3695 ◽  
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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