The protective role of endogenous cytokines in host resistance against an intragastric infection with Listeria monocytogenes in mice (original) (raw)
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Endogenous cytokines during a lethal infection with Listeria monocytogenes in mice
FEMS microbiology …, 1999
It has been demonstrated that endogenous cytokines including Q interferon (IFN-Q), tumour necrosis factor-K (TNF-K), and interleukin-6 (IL-6) play protective roles but that IL-4 and IL-10 play detrimental roles in nonlethal Listeria monocytogenes infection in mice. In this paper, we studied the roles of endogenous cytokines in a lethal infection with L. monocytogenes in mice. TNF-K and IL-6 titres in the bloodstreams, spleens and livers paralleled bacterial numbers in the organs, and both these cytokines and the bacterial numbers peaked just before the mice died. The high titres of TNF-K notably detected in the circulation in lethal infection were different from those in nonlethal infection. The maximum production of IFN-Q was observed before the peaks of TNF-K and IL-6, and IFN-Q almost disappeared from the bloodstreams and organs just before the mice died. No notable difference of IFN-Q titres between lethal infection and nonlethal infection in the specimens obtained from mice was observed. IL-10 was also detected in the bloodstreams earlier than the peaks of TNF-K and IL-6 during lethal infection, while IL-4 was never detected in the sera. The administration of monoclonal antibodies (mAbs) against TNF-K, IFN-Q, IL-6, IL-4 or IL-10 failed to rescue mice from lethal L. monocytogenes infection, whereas anti-TNF-K mAb and anti-IFN-Q mAb prevented mice from lethality by high-dose endotoxin shock. These results suggest that lethality in L. monocytogenes infection might not be determined solely by these cytokines. z
Immunology, 1995
Mice with a secondary Listeria monocytogenes infection eliminate the bacteria much faster and more efficiently from their organs than mice with a primary infection. During the course of a secondary infection, serum concentrations of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF) are higher than during a primary infection. The aim of the present study was to determine whether these cytokines are involved in the acquired resistance to L. monocytogenes during a secondary infection in mice. In order to neutralize cytokines, alginate-encapsulated cells, which form anti-cytokine monoclonal antibodies, were injected into the nuchal region of mice during a Listeria infection. Mice recovered from a sublethal primary Listeria infection, which acquired cell-mediated immunity, received a subcutaneous injection of anti-IFN-gamma-forming cells, or anti-TNF-forming cells, and 4 days later received an intravenous injection with 10 50% lethal dose (LD50) L. monocytogenes. The nu...
Infection and Immunity, 2005
Although the essential role of tumor necrosis factor (TNF) in resistance to Listeria monocytogenes infection is well established, the roles of the related cytokines lymphotoxin alpha (LTα) and lymphotoxin beta (LTβ) are unknown. Using C57BL/6 mice in which the genes for these cytokines were disrupted, we examined the contributions of TNF, LTα, and LTβ in the host response to Listeria . To overcome the lack of peripheral lymph nodes in LTα −/− and LTβ −/− mice, bone marrow chimeras were constructed. TNF −/− and LTα −/− chimeras that lacked both secreted LTα 3 and membrane-bound LTα 1 β 2 and LTα 2 β 1 were highly susceptible and succumbed 4.5 and 6 days, respectively, after a low-dose infection (200 CFU). LTβ −/− chimeras, which lacked only membrane-bound LT, controlled the infection in a manner comparable to wild-type (WT) chimeras. The Listeria -specific proliferative and gamma interferon T-cell responses were equivalent in all five groups of infected mice (LTα −/− and LTβ −/− chim...
Roles for Tumor Necrosis Factor and Gamma Interferon in Resistance to Enteric Listeriosis
1998
Listeria monocytogenes normally infects the host by translocating from the intestinal lumen. Experiments were carried out to determine if, when, and where tumor necrosis factor (TNF) and gamma interferon (IFN-␥) function in antibacterial resistance during enteric listeriosis. Groups of normal mice and severe combined immunodeficient (SCID) mice were injected with neutralizing monoclonal antibodies (MAb) specific for each cytokine and then inoculated intragastrically with L. monocytogenes. The course of infection was monitored by enumerating listeriae in gut-associated lymphoid tissues, livers, and spleens. By the third day of infection, bacterial numbers in infected tissues and organs were greatly exacerbated in all mice treated with anti-TNF MAb, whereas bacterial numbers in the organs of mice treated with anti-IFN-␥ MAb did not differ from those present in the respective organs of control mice. However, by the fifth day of infection, bacterial numbers in the organs of anti-IFN-␥ MAb-treated normal mice and SCID mice were much greater than in the corresponding organs of control mice. Experiments with Listeria-immune mice revealed that TNF and IFN-␥ are involved in the expression of anti-Listeria memory immunity; however, it was also found that the anti-IFN-␥ MAb was relatively ineffective in inhibiting the expression of anti-Listeria immunity, whereas a polyclonal anti-IFN-␥ was quite effective.
Scandinavian Journal of Immunology, 1998
Interleukin-4 (IL-4), a cytokine produced by T-helper 2 (Th2) cells, can inhibit the development of T-helper 1 (Th1) cells, which results in a decreased release of cytokines by the latter. As interferon-g (IFN-g), produced by Th1 cells, is involved in the resistance against a Listeria monocytogenes infection, the role of endogenously formed IL-4 during a Listeria infection in mice was investigated. Neutralization of endogenously formed cytokines by subcutaneously injected alginate-encapsulated monoclonal antibody (MoAb)-forming cells results in high antibody titres in the circulation over a long time period. The aim of the present study was to reevaluate the effect of neutralization of IL-4 during a primary Listeria infection and to investigate the role of IL-4 during a secondary infection in mice using encapsulated MoAb-forming cells. During the course of a primary infection in mice given anti-IL-4 antibody-forming cells (anti-IL-4-FC), the number of Listeria found in the liver and spleen was comparable to that found in control mice given anti-b-galactosidase antibodyforming cells (anti-b-gal-FC). Activation of macrophages measured by inhibition of Toxoplasma gondii proliferation and the release of reactive nitrogen intermediates (RNI) was not affected by anti-IL-4-FC treatment during infection. Furthermore, during a secondary L. monocytogenes infection the number of bacteria in the liver and spleen of anti-IL-4-treated immune mice was comparable to anti-b-gal-FC-treated, control, immune mice. The concentration of IFN-g in plasma of anti-IL-4-treated immune mice was similar to that of control immune mice. Taken together, these findings demonstrate that neutralization of endogenously formed IL-4 does not affect resistance to a primary or a secondary L. monocytogenes infection in mice.
Innate and adaptive immune responses to Listeria monocytogenes: A short overview
The Gram-positive facultative intracellular bacterium Listeria monocytogenes is a model pathogen for elucidating important mechanisms of the immune response. Infection of mice with a sub-lethal dose of bacteria generates highly reproducible innate and adaptive immune responses, resulting in clearance of the bacteria and resistance to subsequent L. monocytogenes infection. Both the innate and adaptive immune systems are crucial to the recognition and elimination of this pathogen from the host.
Infection and immunity, 1996
The production and roles of endogenous interleukin-4 (IL-4) and IL-10 in a sublethal infection with Listeria monocytogenes were studies in normal mice and anti-gamma interferon (IFN-gamma) monoclonal antibody (MAb)-pretreated mice. In normal mice, the expression of mRNAs for IL-4 and IL-10, which was amplified by reverse transcription-PCR, was induced in the spleens and livers either early or late in infection, although the serum IL-4 and IL-10 were not detectable by enzyme-linked immunosorbent assays. In vivo administration of anti-IL-4 MAb showed no effect on antilisterial resistance, whereas anti-IL-10 MAb partially diminished the defense. In anti-IFN-gamma MAb-pretreated mice, a delay in the bacterial elimination from the spleens and livers was observed and high titers of serum IL-4 and IL-10 were induced late in infection. Production of endogenous IL-4 and IL-10 was suppressed in both CD4+ cell-and CD8+ cell depleted mice. The suppression of antilisterial resistance in anti-IFN...
Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Journal of Visualized Experiments, 2011
Listeria monocytogenes (Listeria) is a Gram-positive facultative intracellular pathogen 1. Mouse studies typically employ intravenous injection of Listeria, which results in systemic infection 2. After injection, Listeria quickly disseminates to the spleen and liver due to uptake by CD8α + dendritic cells and Kupffer cells 3,4. Once phagocytosed, various bacterial proteins enable Listeria to escape the phagosome, survive within the cytosol, and infect neighboring cells 5. During the first three days of infection, different innate immune cells (e.g. monocytes, neutrophils, NK cells, dendritic cells) mediate bactericidal mechanisms that minimize Listeria proliferation. CD8 + T cells are subsequently recruited and responsible for the eventual clearance of Listeria from the host, typically within 10 days of infection 6. Successful clearance of Listeria from infected mice depends on the appropriate onset of host immune responses 6. There is a broad range of sensitivities amongst inbred mouse strains 7,8. Generally, mice with increased susceptibility to Listeria infection are less able to control bacterial proliferation, demonstrating increased bacterial load and/or delayed clearance compared to resistant mice. Genetic studies, including linkage analyses and knockout mouse strains, have identified various genes for which sequence variation affects host responses to Listeria infection 6,8-14. Determination and comparison of infection kinetics between different mouse strains is therefore an important method for identifying host genetic factors that contribute to immune responses against Listeria. Comparison of host responses to different Listeria strains is also an effective way to identify bacterial virulence factors that may serve as potential targets for antibiotic therapy or vaccine design. We describe here a straightforward method for measuring bacterial load (colony forming units [CFU] per tissue) and preparing single-cell suspensions of the liver and spleen for FACS analysis of immune responses in Listeria-infected mice. This method is particularly useful for initial characterization of Listeria infection in novel mouse strains, as well as comparison of immune responses between different mouse strains infected with Listeria. We use the Listeria monocytogenes EGD strain 15 that, when cultured on blood agar, exhibits a characteristic halo zone around each colony due to β-hemolysis 1 (Figure 1). Bacterial load and immune responses can be determined at any time-point after infection by culturing tissue homogenate on blood agar plates and preparing tissue cell suspensions for FACS analysis using the protocols described below. We would note that individuals who are immunocompromised or pregnant should not handle Listeria, and the relevant institutional biosafety committee and animal facility management should be consulted before work commences.
FEMS Immunology …, 1995
In vivo induction of cytokines by a monoclonal antibody (mAb) against T-cell receptor (TCR) cyp and the protective effect induced by the mAb on a lethal infection with Listeria monocytogenes were studied. Injection of anti-TCR (YP mAb induced rapid production of endogenous tumour necrosis factor in the spleens, and gamma interferon and interleukin-6 in the bloodstreams and spleens of mice. Administration of anti-CD4 mAb, anti-CD8 mAb, or anti-Thyl.2 mAb resulted in suppression of anti-TCR cr/3 mAb-induced endogenous cytokine production. Mice were protected against lethal L. monocytogenes infection when treated with anti-TCR cwp mAb. The protective effect was not demonstrated in CD4 + cellor CD8 + cell-depleted mice. These results suggest that anti-TCR ap mAb shows a protective effect on a lethal infection with L. monocytogenes in mice and that the mAb-induced endogenous cytokines might be involved in the effect of anti-TCR rub mAb. factor (TNF), gamma interferon (IFN-71, interleukin-1 (IL-l), IL-6, and colony-stimulating factors has been reported for L. monocytogenes-infected mice [3-71. Studies including in vivo administration of monoclonal antibodies (mAbs) against cytokines and gene knockout technology demonstrated that TNF and IFN-y are crucial in antilisterial resistance [8-141. We previously reported that an anti-CD3 mAb protected mice against a lethal infection with L. monocytogenes through induction of endogenous 092%8244/95/$09.50 0 1995 Federation of European Microbiological Societies. All rights reserved SSDI 0928-8244(95)00040-2