Endogenous interleukin-4, but not interleukin-10, is involved in suppression of host resistance against Listeria monocytogenes infection in interferon-depleted mice (original) (raw)
Related papers
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.
Infection and Immunity, 2000
The aim of this study was to investigate the effect of interleukin-10 (IL-10) on the course of Listeria monocytogenes infection in naive and immune mice. Treatment with IL-10 during the course of a primary infection significantly decreased the number of bacteria in the spleen and did not affect the number in the liver. During a secondary infection in immune mice treated with IL-10, the number of bacteria was significantly lower in the spleen but significantly higher in the liver in comparison to mock-treated immune mice. IL-10 treatment during a primary Listeria infection decreased the concentration of gamma interferon (IFN-␥) in plasma and the toxoplasmastatic activity of macrophages, whereas it increased the percentage of mildly CD3-positive T cells in the spleen. During a secondary infection, the concentration of IFN-␥ in plasma was decreased on day 1 but remained unaffected during later days of infection. From these results, we conclude that IL-10 has different effects on the proliferation of L. monocytogenes in the spleen and liver during primary and secondary Listeria infections.
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.
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...
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
Surface interleukin-10 inhibits listericidal activity by primary macrophages
Journal of leukocyte biology, 1999
Interleukin-10 (IL-10) down-regulates multiple functions of monocytes and macrophages, including the ability of macrophages to kill many intracellular microorganisms. The experiments presented here test the hypothesis that IL-10 expressed on the cell surface inhibits the ability of primary mouse macrophages to kill the facultative, intracellular bacterium Listeria monocytogenes. We show that, in contrast to macrophages from normal mice, both bone marrow-derived macrophages (BMDM) and thioglycollate-elicited macrophages obtained from IL-10-/- mice can kill L. monocytogenes. Treatment with anti-IL-10 monoclonal antibody (mAb) enables BMDM from normal mice and thioglycollate-elicited macrophages from RAG-2-/- mice (which lack T or B cell-derived IL-10) to kill L. monocytogenes, and concurrently down-regulates the expression of surface IL-10. Surface IL-10 on paraformaldehyde-fixed cells can inhibit nitric oxide (NO) production by interferon-gamma (IFN-gamma)-stimulated macrophages from...
Blocking the Receptor for Interleukin 10 Protects Mice from Lethal Listeriosis
Antimicrobial Agents and Chemotherapy, 2001
High doses of Listeria monocytogenes overcome the ability of a normal mouse to control the infection, due to massive bacterial replication. Treatment with an anti-interleukin 10 (IL-10) receptor monoclonal antibody prevented the fatal course of infection with high doses of bacteria. This work shows that blocking the receptor for IL-10 may have useful therapeutic applications.
Infection and Immunity, 2001
To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10 ؊/؊ ) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis. IL-10 ؊/؊ mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10 ؊/؊ mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages. IL-10 ؊/؊ mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1␣ [MIP-1␣], and MIP-1) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8 ؉ T cells were reduced and the intracerebral bacterial load was not reduced in IL-10 ؊/؊ mice compared to WT mice. Following intraperitoneal infection, IL-10 ؊/؊ mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.