Search PubMed⌕ Search

Biomedical subjects

M M Stevenson

Publications and source records attributed to M M Stevenson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization of chronic bronchopulmonary Pseudomonas aeruginosa infection in resistant and susceptible inbred mouse strains.

Chronic bronchopulmonary Pseudomonas aeruginosa infection, initiated by intratracheal instillation of 1 to 2 x 10(5) colony-forming units of a mucoid strain of bacteria trapped in agar beads, was characterized in resistant BALB/c mice and susceptible C57BL/6 (B6) mice through 28 d postinfection. B6 mice experienced a more severe infection than BALB/c mice as evidenced by significantly higher mortality and significantly greater weight loss during the first 14 d. Furthermore, B6 mice had significantly higher numbers of bacteria in the lungs through 21 d after infection. Overall, only 22% of these hosts cleared the infection. In contrast, 67% of BALB/c mice cleared the infection. These differences between resistant and susceptible mice were found to correlate with histopathologic differences in the type of inflammation and the extent of tissue damage. An acute, predominantly neutrophilic inflammation and extensive tissue damage were apparent in the lungs of susceptible B6 mice, whereas chronic, granulomatous inflammation and little or no tissue damage were visible in resistant BALB/c mice. The finding of acute inflammation in the lungs of infected B6 mice was confirmed by fluorescence-activated cell sorter (FACS) analyses, which demonstrated that these mice had significantly greater proportions of polymorphonuclear neutrophils in the lungs on Days 7 and 14 after infection than did BALB/c mice. FACS analyses also revealed significant and similar increases in CD3(+) lung cells in both strains as the infection progressed. The CD4/CD8 ratio was significantly greater in BALB/c mice by 21 d after infection when the majority of these animals, but not B6 mice, had cleared the infection.

Animals↗
PubMed1998

Dietary protein and zinc restrictions independently modify a Heligmosomoides polygyrus (Nematoda) infection in mice.

The effects of dietary protein and zinc restrictions on Heligmosomoides polygyrus were compared following primary and challenge infection in female BALB/c mice fed either control (24%), marginal (7%) or low (3%) protein combined with either high or low zinc (60 or 3 mg Zn/kg diet). Dietary protein restriction (3%) resulted in significantly lower body weight gain. As well, blood urea nitrogen (BUN) significantly decreased with decreasing dietary protein level. However, neither plasma albumin concentration nor relative thymus or spleen weights were reduced. Marginal zinc deficiency was confirmed by significantly lower tibia and liver zinc concentration, but food intake, body weight gain, relative thymus and spleen weights, and alkaline phosphatase activity were not altered. On day 29 post-primary infection, worm burdens were significantly higher in mice fed either marginal or low protein and in mice fed a low zinc diet, while parasite egg output was significantly higher in mice fed both low protein and low zinc diet. Immune status was compromised in mice fed low protein (significantly lower serum IgG1 and lower eosinophilia), and in mice fed low zinc diet (significantly lower eosinophilia). Early in the infection, IgE titres were elevated in mice fed low protein or low zinc, but IgE titres declined to levels lower that the control diet groups after 14-21 days. On day 29 post-challenge infection, worm burdens and parasite egg output were significantly higher in mice fed low protein, whereas the other group had expelled almost all parasites. Dietary restriction had no effect on IgE. Significantly reduced serum IgG1 titres and eosinophilia in mice fed 3% protein supported the view that low dietary protein but not low zinc increased host susceptibility to H. polygyrus by compromising host immune function following reinfection in immunized mice.

Animals↗
PubMed1998

Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production.

Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro, IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro, the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.

Anemia↗
PubMed1998

Energy restriction and zinc deficiency impair the functions of murine T cells and antigen-presenting cells during gastrointestinal nematode infection.

This study examined whether the impaired immune responses in zinc deficient- and/or energy-restricted mice exposed to a challenge infection of Heligmosomoides polygyrus might be associated with reduced numbers of spleen cells, altered proportions of spleen cell subpopulations and/or altered function of the T cells or antigen-presenting cells (APC). Female BALB/c mice were given free access to either a zinc-sufficient (60 mg zinc/kg diet, Zn+) or a zinc-deficient diet (0.75 mg zinc/kg diet, Zn-) or were pair-fed (PF) the zinc-sufficient diet. Significant differences in parasite burdens were observed. Worm numbers were lowest in Zn+ mice, intermediate in the PF mice and highest in the Zn- mice, showing that both zinc deficiency and energy restriction reduced protective immunity against the gastrointestinal nematode H. polygyrus. Although the absolute numbers of spleen cells were reduced in both Zn- and energy-restricted (PF) mice, neither deficiency altered the phenotypic distribution of the subpopulations of positive marker cells in the spleen. In vitro functional assays using a 1:1 ratio of APC:T cells showed that T-cell proliferation in response to parasite antigen (Ag) was impaired by a dietary effect of zinc deficiency on T cells and of energy restriction and zinc deficiency on APC function. Consequences of the nutritional deficiencies on cytokine production in response to parasite antigen were more complex: zinc deficiency reduced T-cell function [interleukin-4 and interleukin-5 (IL-4 and IL-5) production], and both nutritional deficits depressed APC functions [IL-4, IL-5, and interferon-gamma (IFN-gamma) production] and T-cell function (IFN-gamma production). Thus, this study showed that zinc deficiency and energy restriction played identifiably distinct roles in regulating host immune responses against the gastrointestinal nematode H. polygyrus.

Animals↗
PubMed1998

Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa.

The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftrunc/Cftrunc knockout [B6-Cftr (-/-)] mice to pulmonary infection with Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr (-/-) mice died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr (-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or age of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr (-/-) knockout mice and their littermate controls developed similar lung pathology during the course of infection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lung infection resulting in a dramatically increased mortality rate and higher bacterial load.

Animals↗
PubMed1998

Interleukin-12 corrects severe anemia during blood-stage Plasmodium chabaudi AS in susceptible A/J mice.

The in vivo role of interleukin (IL)-12 in correcting anemia and the underlying defect in erythropoiesis in Plasmodium chabaudi AS-susceptible A/J mice was examined. Six daily intraperitoneal injections of 0.1 microg IL-12 in A/J mice, beginning on the day of infection, rapidly and significantly enhanced bone marrow and splenic erythropoiesis as demonstrated by marked increases in early and late committed erythroid progenitors, the erythroid burst (BFU-E) and colony-forming units (CFU-E), respectively, compared with control mice. The most dramatic effect of IL-12 treatment was a sevenfold increase in the number of splenic CFU-E on day 7 postinfection, compared with untreated, infected A/J mice. Treatment with IL-12 also caused significant increases in hematocrit levels, erythrocyte counts, percentage of reticulocytes, spleen cellularity, and frequencies of BFU-E and CFU-E in the bone marrow and spleen of A/J mice during infection. The frequency of BFU-E in the peripheral blood of these mice was also significantly increased, suggesting enhanced mobilization of precursor cells to the spleen as well as increased production of erythroid precursors in this organ. Consistent with previous observations using higher doses, 0.1 microg IL-12 administered daily for 6 days to normal A/J mice significantly decreased bone marrow erythropoiesis and significantly increased splenic erythropoiesis. However, the influence of IL-12 on erythropoiesis was much more pronounced during ongoing malaria infection. These results suggest a role for IL-12 during blood-stage malaria in not only enhancing the development of protective immunity but also in alleviating malaria-induced anemia by increasing the number of erythroid precursors and enhancing the expansion of committed erythroid progenitors.

Anemia↗
PubMed1997

Natural killer cell cytokine production, not cytotoxicity, contributes to resistance against blood-stage Plasmodium chabaudi AS infection.

Our recent study showed that IL-12 treatment of susceptible A/J mice induces Th1-mediated, protective immunity against lethal blood-stage Plasmodium chabaudi AS infection. To further understand the mechanism of this protection, we examined NK cell cytotoxic (NKCC) and cytokine secretory functions in untreated and IL-12-treated A/J mice, along with resistant C57BL/6 (B6) mice. Normal A/J mice receiving six daily doses of 0.1 microg IL-12 exhibited significant increases in NKCC in total spleen cell populations. Defective NKCC evident in vitro in enriched NK cells from infected A/J mice was corrected by addition of 10 ng/ml IL-12 and was comparable with that seen in B6 mice. In vivo and in vitro analyses revealed that enriched NK cells from day 6 infected A/J mice were defective not only in NKCC, but also in IFN-gamma, and to a certain extent, TNF-alpha secretion, which could also be corrected by IL-12 treatment. Depletion of NK cells from resistant B6 mice resulted in a more severe course of infection, while NK cell-depleted, IL-12-treated A/J mice had significantly higher parasitemia, as well as 100% mortality, suggesting the importance of NK cells in IL-12-mediated protection. NKCC-defective bg/bg mice produced optimum IFN-gamma and TNF-alpha and recovered from infection similar to bg/+ controls; in vivo depletion of these cytokines resulted in significantly higher parasitemia early in infection. Based on these results, we conclude that IFN-gamma, and possibly TNF-alpha, secretion by NK cells during early infection plays a major role in protective immunity to blood-stage malaria.

Adjuvants, Immunologic↗
PubMed1997

Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda).

This study characterized the consequences of zinc-sufficient (Zn+, 60 mg zinc/kg diet, ad libitum), zinc-deficient (Zn-075 mg zinc/kg diet, ad libitum) and energy-restricted (ER, 60 mg zinc/kg diet which was restricted to match food intake of Zn- mice) diets on the in vivo and in vitro immune response of BALB/c mice during both primary and challenge infection with Heligmosomoides polygyrus. In Zn+ mice, both primary and challenge infection with H. polygyrus induced not only a strong Th2 response (IgE, IgG1, eosinophilia, IL-4, IL-5, IL-10), but also elements of a TH1 response (IgG3, IFN-gamma). Zinc deficiency significantly depressed Th2-dependent antibody production during both primary and challenge infection, and reduced mitogen and antigen-induced T cell proliferation during the challenge infection. Th2 cytokine production was reduced by zinc deficiency (IL-4), energy restriction (IL-5) and by zinc deficiency possibly in combination with energy restriction (IL-10) during the primary infection whereas TH1 cytokine production (IFN-gamma) was depressed during the challenge infection by zinc deficiency, possibly together with energy restriction. Both zinc deficiency and energy restriction reduced eosinophilia with the more profound effect being exerted by zinc deficiency. Thus, both zinc deficiency and its concurrent energy restriction modify immune responses in the mice during primary and challenge infection with H. polygyrus.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Differential clearance of glycoforms of IgG in normal and autoimmune-prone mice.

In order to understand better the origins of the elevated levels of the glycoform of IgG that lacks galactose on both arms of the oligosaccharide chain (G0%) located in the Fc, which occurs in man and mouse with age, and in particular in autoimmune disease, we investigated the clearance of two glycosylated forms of IgG2a and IgG1 in normal (BALB/c) and autoimmune-prone (MRL/1pr, MRL/+, and non-obese diabetic (NOD)) mice. To investigate the possibility of different rates of catabolism, enzymatically generated glycoforms of monomeric IgG1 and IgG2a (fully glycosylated or G0%), were iodinated and injected into the tail vein of the mice. We found that the G0% IgG2a remained in circulation significantly longer than the fully glycosylated variants, in all of the mouse strains tested. In contrast, the two forms of IgG1 had similar kinetics in all the autoimmune-prone mice, whereas in BALB/c, there was a longer half-life (t1/2) for G0% IgG1. These data suggest that there may be differences in the ability of the IgG glycoforms to bind to the Fc gamma receptors, in particular Fc gamma RI. The clearance rates were found to vary among the strains studied, with MRL/1pr having the fastest catabolic rates for all glycoforms and IgG subclasses tested. This appeared to be due to the presence of circulating IgG and IgM rheumatoid factors (RF). There were significantly increased frequencies and titres for both IgM and IgG RF in MRL/1pr mice compared with the other strains. In contrast, interferon-gamma, known to induce the Fc gamma RI, was found to be similar in the sera, in all of the strains of mice examined. These results suggest that RF probably play an important biological function in the MRL/1pr mice and aid in the clearance of circulating IgG. Our study shows that the state of glycosylation of IgG affects the t1/2 in vivo, and that by removing the terminal sugars (sialic acid and galactose), the antibody (IgG2a) will remain in circulation significantly longer. These observations may thus provide a partial explanation for the increase in relative percentage of this glycoform that occurs with age.

Animals↗
PubMed1996

In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice.

We investigated whether gamma interferon (IFN-gamma; a Th1 cytokine), tumor necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4; a Th2 cytokine) modulate nitric oxide (NO) production in vivo during blood stage infection with Plasmodium chabaudi AS. Treatment of resistant C57BL/6 mice, which resolve infection with P. chabaudi AS and produce increased levels of IFN-gamma, TNF-alpha, and NO early during infection, with anti-IFN- gamma plus anti-TNF-alpha monoclonal antibodies (MAbs) resulted in a reduction of both splenic inducible NO synthase mRNA and serum NO3- levels by 50 and 100%, respectively. Treatment with the anti-TNF-alpha MAb alone reduced only serum NO3- levels by 35%, and treatment with the anti-IFN-gamma MAb alone had no effect on NO production by these mice during infection. Susceptible A/J mice, which succumb to infection with P. chabaudi AS and produce increased levels of IL-4 but low levels of IFN-gamma, TNF-alpha, and NO early during infection, were treated with an anti-IL-4 MAb. The latter treatment had no effect on NO production by this mouse strain during infection. In addition, our results also demonstrate that treatment of resistant C57BL/6 mice with anti-IFN-gamma plus anti-TNF-alpha MAbs affects, in addition to NO production, other traits of resistance to P. chabaudi AS malaria such as the peak level of parasitemia and the development of splenomegaly. Furthermore, the change in spleen weight was shown to be an IFN-gamma-independent effect of TNF-alpha. Treatment of susceptible A/J mice during infection with an anti IL-4 MAb had no effect on these markers of resistance. Thus, these results demonstrate that TNF-alpha and IFN-gamma are critical in the regulation of NO production and other traits of resistance during P. chabaudi AS malaria in C57BL/6 mice. These data also indicate that treatment with an anti-IL-4 antibody alone is not able to induce NO production or confer resistance to A/J mice against P. chabaudi AS malaria.

Animals↗
PubMed1996

A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice.

We investigated the kinetics of tissue-specific mRNA expression and systemic production of tumor necrosis factor alpha (TNF-alpha) and the kinetics of splenic expression of mRNAs of gamma interferon (INF-gamma) and interleukin-4 (IL-4), cytokines that may regulate TNF-alpha production, during the early phase of blood-stage infection with Plasmodium chabaudi AS. Northern blot analysis revealed that resistant C57BL/6 mice, which clear the infection by 4 weeks, had higher levels of TNF-alpha mRNA in the spleen and liver early during infection that did susceptible A/J mice, which succumb to the disease 10 days after initiation of infection. Treatment of resistant mice with a polyclonal anti-TNF-alpha antibody confirmed the protective role of TNF-alpha early during the course of infection. Furthermore, resistant C57BL/6 mice also expressed high levels of mRNA of IFN-gamma (a Th1 marker) and low levels of mRNA of IL-4 (a Th2 marker) in the spleen, whereas susceptible A/J mice had low levels of IFN-gamma mRNA but high levels of TNF-alpha mRNA in the liver and had high levels of TNF-alpha protein in serum, as measured by enzyme-linked immunosorbent assay, later during infection just before death occurred. These results demonstrate that a Th1-associated increase in TNF-alpha mRNA expression in the spleen early during infection correlates with resistance to P. chabaudi AS, whereas increased TNF-alpha mRNA levels in the liver and excessive levels of the TNF-alpha protein in serum later during infection correlate with susceptibility. Thus, the role of the TNF-alpha during malaria appears to depend on the timing and site of its expression and the presence of cytokines regulating its production.

Animals↗
PubMed1995

Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice.

The production and function of nitric oxide during the early phase of blood-stage infection with Plasmodium chabaudi AS was analyzed using two inbred strains of mice that differ in the level of resistance to this parasite. Northern blot analysis of in vivo expression of inducible nitric oxide synthase (iNOS) revealed that early during infection resistant C57BL/6 mice, which clear the infection by 4 wk, have higher levels of iNOS mRNA in the spleen than susceptible A/J mice. In contrast, susceptible A/J mice have significantly increased levels of iNOS mRNA in the liver later in the course of infection just before death occurs. Splenic macrophages recovered from resistant C57BL/6 mice on day 7 postinfection express iNOS mRNA which is up-regulated following overnight stimulation of the cells with LPS. Furthermore, during the first week postinfection, splenic macrophages recovered from resistant hosts produce significantly higher levels of nitrite (NO2-) in vitro in response to LPS than similarly stimulated macrophages from susceptible A/J mice. Increased levels of nitrate (NO3-) were only detected in serum of resistant C57BL/6 mice at the time of peak parasitemia. Treatment with the iNOS inhibitor, aminoguanidine, reduced NO3- levels in serum of C57BL/6 mice and eliminated resistance of these hosts to P. chabaudi AS malaria without affecting parasitemia. These results demonstrate that the ability to produce high amounts of nitric oxide (NO) early during infection with blood-stage P. chabaudi AS correlates with resistance, but that NO may not be involved in parasite killing. Moreover, the tissue site of NO production, that is, spleen vs liver, appears to be critical and correlates with resistance vs susceptibility to P. chabaudi AS malaria, respectively.

Animals↗
PubMed1995

IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism.

The effects of IL-12 administration on the development of protective immunity to blood-stage Plasmodium chabaudi AS were analyzed. Treatment of susceptible A/J mice on the day of infection and for 5 days postinfection with various doses 0.025-0.3 microgram) of rIL-12 significantly decreased the peak parasitemia level, but only treatment with 0.1 microgram resulted in increased survival. Treatment of resistant B6 mice with 0.1 microgram of rIL-12 using the same regimen also significantly decreased the peak parasitemia level, but 40% of the animals died. Treatment of these mice with anti-IL-12 mAb resulted in a more severe course of infection, but survival was not significantly altered. The mechanism of IL-12-induced resistance was examined in A/J mice during infection. Compared with spleen cells from untreated mice, cells from IL-12-treated mice produced significantly higher levels of IFN-gamma spontaneously as well as in response to Con A or Ag stimulation on day 7 postinfection. Significantly higher levels of INF-gamma and TNF-alpha were found in the sera of IL-12-treated mice, which correlated with high levels of the nitric oxide (NO) metabolite, NO3-. Furthermore, CD4+T cell depletion was found to abrogate IL-12-induced resistance. Administration of neutralizing mAb against IFN-gamma or TNF-alpha to IL-12-treated mice showed that simultaneous depletion of both cytokines resulted in 100% mortality. The role of NO was investigated by administration of aminoguanidine, a selective inhibitor of cytokine-inducible nitric oxide synthase, to IL-12-treated mice. Significantly increased mortality was observed following treatment twice daily with 9 mg of aminoguanidine, but there was no effect on parasitemia. In conclusion, these results demonstrate that IL-12 regulates the development of resistance to P. chabaudi AS via a CD4+ Th1 response, which involves the cytokines IFN-gamma and TNF-alpha, and is in part NO dependent. Therefore, IL-12, given in the appropriate dose, may be useful in the induction of protective immunity to blood-state malaria.

Animals↗
PubMed1995

Role of macrophage-derived nitric oxide in suppression of lymphocyte proliferation during blood-stage malaria.

Examination of the proliferative responses in vitro to mitogens (concanavalin A, phytohemagglutinin, lipopolysaccharide) of spleen cells recovered from C57BL/6 mice during blood-stage Plasmodium chabaudi AS infection revealed that the most severe suppression occurred during the first 14 days post infection, that is, during the acute phase of infection. Coincidently, inducible nitric oxide synthase gene expression was found to be up-regulated in the spleens of infected mice, and both splenic and peritoneal macrophages produced high levels of NO in vitro in response to stimulation with lipopolysaccharide (LPS). The roles of NO, a molecule recently found to mediate immunosuppression during parasitic infections, and of the well-recognized immunosuppressive molecule prostaglandin were, therefore, investigated in the suppression of proliferation to mitogens and specific antigen of spleen cells from 7- and 14-day P. chabaudi AS-infected mice. Addition of either 0.5 mM NG-monomethyl-L-arginine (L-NMMA) or 0.5 mM aminoguanidine (AG), inhibitors of NO synthase, or 10 micrograms/ml indomethacin (INDO), a prostaglandin inhibitor, partially but significantly abrogated the suppression in response to concanavalin A (Con A) and phytohemagglutinin (PHA). Only the addition of INDO significantly increased the responses to LPS. Addition of L-NMMA or AG in combination with INDO partially but significantly abrogated the suppression in response to Con A and completely abrogated the suppression in response to PHA. The addition of L-NMMA or AG also significantly increased proliferation in response to parasite antigen. The contribution of NO to suppression of lymphoproliferation was confirmed by adding 3-morpholino-sydnonimine-hydrochloride (SIN-1), a chemical generator of NO, to mitogen-stimulated splenocyte cultures prepared from normal mice. The mechanism of NO-mediated suppression was investigated in coculture experiments using spleen cells from normal mice and peritoneal macrophages from either normal or day 7 infected mice. The addition of 5-10 x 10(4) peritoneal macrophages from infected mice significantly and consistently suppressed Con A- or PHA-stimulated proliferation of normal splenocytes. Moreover, suppression correlated with production of NO and could be reversed by the addition of L-NMMA or AG. These results suggest that, in addition to prostaglandin, increased NO production by macrophages within the first 2 weeks after infection with P. chabaudi AS contributes to immunosuppression associated with blood-stage malaria.

Amino Acid Oxidoreductases↗
PubMed1995

Energy restriction and severe zinc deficiency influence growth, survival and reproduction of Heligmosomoides polygyrus (Nematoda) during primary and challenge infections in mice.

The objectives of this study were (1) to determine the impact of severe zinc deficiency on the establishment, growth, survival and reproduction of Heligmosomoides polygyrus in the laboratory mouse, during both primary and challenge infection protocols, and (2) to determine whether the observed effects resulted from zinc deficiency per se, or from the accompanying energy restriction. Three diet groups were used: zinc-sufficient (Zn+:60 mg zinc/kg diet), zinc-deficient (Zn-:0.75 mg zinc/kg diet) and energy restricted (ER:60 mg zinc/kg diet pair fed to Zn- mice). Neither Zn- nor ER influenced the establishment of the parasite during a primary infection. However, both significantly influenced the early development of the parasite. The proportion of adult worms recovered 9 days post-infection (p.i.) was highest in Zn- mice, intermediate in ER mice and lowest in Zn+ mice. Worms were also distributed more distally in the intestine of the Zn- mice and worm survival was highest in Zn- mice, intermediate in ER mice and lowest in Zn+ mice at both 4 and 5 weeks p.i. Although the length of female worms was reduced in Zn- mice, neither per capita fecundity nor egg viability was affected by zinc deficiency. Energy restriction, on the other hand, significantly reduced worm fecundity at 5 weeks post-primary infection, but had no effect on egg viability. Zinc concentration of adult H. polygyrus was similar among dietary groups. The effects of zinc deficiency and energy restriction were also investigated 4 and 5 weeks after a challenge infection. Whereas strong host resistance was evident in Zn+ and ER mice, based on comparison of worm numbers between challenged mice and primary infection controls, no evidence of resistance was detected in Zn- mice. As in the primary infection, female worms were shorter in Zn- mice than in ER and Zn+ mice, and energy restriction but not zinc deficiency significantly affected per capita fecundity. However, in contrast to the primary infection, ER mice had elevated rather than reduced fecundity. This study demonstrates a complex interaction between H. polygyrus and zinc and energy restriction, and highlights the importance of controlling for reduced food intake in nutrition-infection studies.

Animals↗
PubMed1995

In vitro and in vivo T cell responses in mice during bronchopulmonary infection with mucoid Pseudomonas aeruginosa.

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.

Animals↗