Selenium deficiency impairs host innate immune response and induces susceptibility to Listeria monocytogenes infection.

BACKGROUND: Susceptibility or resistance to infection with Listeria monocytogenes correlates with Selenium (Se) deficiency in response to infection. RESULTS: Se-deficient mouse models of listeriosis were used to study the innate immune response during the course of L. monocytogenes infection. Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Intestine, mesenteric lymph node, liver, spleen and brain from each mouse were to study the bacterial burden in organs. The analysis of cell types of spleen from Se-deficient mice revealed that the ability of the host to elicit a rapid recruitment and activation of systemic innate immune response to infection was to a certain extent compromised under conditions of Se deficiency. The cytokine levels in the serum and cytokine expression levels in the livers from Se-deficient mice revealed that the innate immune response of Se-deficient mice was impaired throughout the course of infection. These results suggest that innate immune response is altered by Se deficiency after infection with L. monocytogenes. CONCLUSION: In conclusion, induced susceptibility of host resistance is associated with an impaired innate immune response following infection with L. monocytogenes in C57BL/6 Se-deficient mice.

Assessment of interleukin-12, gamma interferon, and tumor necrosis factor alpha secretion in sera from mice fed with dietary lipids during different stages of Listeria monocytogenes infection.

Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-gamma, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-alpha production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-gamma production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.

Ability of orally administered IFN-alpha-containing transgenic potato extracts to inhibit Listeria monocytogenes infection.

Type I interferons (IFN-alpha/beta) were originally thought to be antiviral cytokines, but it has recently been reported that they also play an important role in potentiating innate and adaptive immune responses. Moreover, several studies have shown that the oral administration of type I IFN ameliorates various biologic activities. Here, we studied the ability of orally administered IFN-alpha to protect mice from systemic Listeria monocytogenes infection. Daily oral administration of purified natural IFN-alpha at a concentration of 1000 international units (IU)/20 microl reduced the bacterial burden in infected organs. We also examined the protective effect of IFN-alpha expressed in transgenic potato plants. A much lower concentration of IFN-alpha (20 IU/ 20 microl) in the plant extracts was almost as protective as much higher concentrations of purified natural IFN-alpha. Our observations indicate that transgenic cytokine-expressing plants can be used prophylactically as edible pharmaceuticals to enhance systemic defense responses in humans and animals.

Uncaria tomentosa extract increases the number of myeloid progenitor cells in the bone marrow of mice infected with Listeria monocytogenes.

In this study, we demonstrated that Uncaria tomentosa extract (UTE) protects mice from a lethal dose of Listeria monocytogenes when administered prophylactically at 50, 100, 150 and 200 mg/kg for 7 days, with survival rates up to 35%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with L. monocytogenes, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Non-infected mice treated with 100 mg/kg UTE also presented higher numbers of CFU-GM in the bone marrow than the controls. Investigation of the production of colony-stimulating factors revealed increased colony-stimulating activity (CSA) in the serum of normal and infected mice pre-treated with UTE. Moreover, stimulation of myelopoiesis and CSA occurred in a dose-dependent manner, a plateaux being reached with the dose of 100 mg/kg. Further studies to investigate the levels of factors such as IL-1 and IL-6 were undertaken. We observed increases in the levels of IL-1 and IL-6 in mice infected with L. monocytogenes and treated with 100 mg/kg of UTE. White blood cells (WBC) and differential counting were also performed, and our results demonstrated no significant changes in these data, when infected mice were pre-treated with 100 mg/kg of UTE. All together, our results suggest that UTE indirectly modulates immune activity and probably disengages Listeria-induced supression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1 and IL-6).

Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine interleukin-12 and interferon-gamma production in vivo.

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.

Protective effect of a traditional Japanese medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to), on the restraint stress-induced susceptibility against Listeria monocytogenes.

In this study, the effect of traditional Japanese (Chinese) medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT), on the restraint stress treatment (RST)-induced susceptibility against Listeria monocytogenes (L. monocytogenes) was examined. When RST was performed every day for 10 h from the day of infection, the bacterial numbers were increased at 3 and 5 days after the infection. Oral pretreatment with HOT for 7 days prevented such increases. Pretreatment with HOT prevented the suppression of antigen-specific IFN-gamma production by RST. HOT also prevented suppression of macrophage accumulation, including MHC-class II positives, in the peritoneal cavity and their bactericidal activity by RST. HOT suppressed the serum corticosterone level elevated by RST in infected mice. Taken together, the suppression of corticosterone using HOT participates in the prevention of suppressions of the bactericidal activity of macrophages, migration of macrophages and antigen-specific IFN-gamma production of Th1 cells by RST. Our findings suggest that HOT is a useful drug for patients suffering from stress disease to reduce the susceptibility to bacterial infection.

Effects of Chlorella vulgaris on bone marrow progenitor cells of mice infected with Listeria monocytogenes.

In this study we investigated the effects of the treatment with Chlorella vulgaris extract (CVE) on the hematopoietic response of granulocyte-macrophage colony-forming unit (CFU-GM) of mice infected with a sublethal dose of Listeria monocytogenes (1 x 10(4) organisms/animal). CVE was given orally as 50 mg/kg/day for 5 days. In the CVE treated/infected groups L. monocytogenes was administered at the end of CVE treatment. The colony stimulating activity of the serum (CSA) was also studied in all groups. Although no effects on CFU-GM, as compared to controls, were observed in the groups receiving CVE alone, the extract produced an increase in CSA levels as compared to controls. On the other hand, the presence of the infection led to a significant reduction in the numbers of CFU-GM as observed at 48 and 72 h after the infection, in spite of the significant increase in serum CSA activity. CVE treatment of infected animals restored the numbers of CFU-GM to control levels. In the treated/ infected group the increased serum CSA was significantly higher than that observed in the only infected group. The CVE treatment (50 and 500 mg/kg) of mice infected with a dose of 3 x 10(5) bacteria/animal, which was lethal for all the non-treated controls, produced a dose-response protection which led to a 20 and 52% survival, respectively. These results demonstrated that CVE produces a significant increase in the resistance of the animals infected with L. monocytogenes, and that this protection is due, at least in part, to increased CFU-GM in the bone marrow of infected animals.