Antibody in host defense against mouse pneumonitis agent (murine Chlamydia trachomatis).

In a murine model of chlamydial pneumonia employing murine Chlamydia trachomatis, immune serum given intranasally delayed death in nude (nu/nu) mice and prevented death in nu/+ mice. Serum-derived immunoglobulin G and A fractions and immune lavage fluid fractions containing immunoglobulins G and A were effective in producing protection when used to opsonize the murine C. trachomatis inoculum. In hyperclean mice (previously made germfree and then colonized with a limited flora nonpathogenic to mice) antibody given intravenously was ineffective. The effects of antibody and nonspecific stimulation of cell-mediated immunity (after previous infection with Histoplasma capsulatum) were additive in increasing host resistance to murine C. trachomatis.     

Immune response in mice infected in the genital tract with mouse pneumonitis agent (Chlamydia trachomatis biovar).

Female Swiss-Webster mice were inoculated intravaginally with mouse pneumonitis agent (MoPn), a Chlamydia trachomatis biovar. Inoculation with 3.5 X 10(5) egg lethal doses per mouse resulted in shedding of the agent from the genital tract for as long as 21 days. Immunoglobulin M antibodies to MoPn were detected in plasma by day 7 post-inoculation, and immunoglobulin G antibodies were detected by day 14. Antibodies were detected in genital secretions by day 20, and titers in plasma and secretions were still considerable on day 56. Delayed-type hypersensitivity tests, determined by footpad swelling, were not positive in appreciable numbers of animals until after day 25. Delayed-type hypersensitivity reactions were maximal 24 h after testing and were preceded by an Arthus-like reaction, which appeared within 3 h and declined by 12 h. Convalescent animals were rechallenged by intravaginal inoculation and were found to be solidly immune.     

Adjuvant activity of all-trans-retinoic acid in C57Bl/6 mice.

The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals.     

Intravaginal inoculation of mice with the Chlamydia trachomatis mouse pneumonitis biovar results in infertility.

In an attempt to establish a model of chlamydial ascending salpingitis and infertility, three inbred strains of mice, C3H/HeN (H-2k), C57BL/6N (H-2b), and BALB/cAnN (H-2d), were inoculated intravaginally with 3 x 10(7) inclusion-forming units of the Chlamydia trachomatis mouse pneumonitis biovar. Mice mated 6 weeks following inoculation were found to have a significant decrease in fertility rate compared with the control groups, as shown by a reduction in the number of pregnant mice and a decrease in the number of embryos.     

Local immune response to Mycobacterium lepraemurium in C3H and C57Bl/6 mice.

Subcutaneous footpad inoculation of living M. lepraemurium (L.MLM) induced, in high responder C57Bl/6 mice, a local granulomatous reaction associated with the production of effector cells which stopped the multiplication of bacilli in the draining popliteal node with the concurrent development of 24--48 hr delayed type hypersensitivity (DTH). The thymus-dependent local reaction did not occur after the injection of heat-killed M. lepraemurium (HK.MLM) or after the inoculation of L.MLM in nude mice. However, HK.MLM injection interfered with the onset of the local reaction and enhanced acid-fast bacteria (AFB) counts in the draining node. In low responder C3H mice, L.MLM produced a local and delayed footpad swelling but no restriction of bacilli multiplication in the draining lymph node was observed. This unresponsiveness was not due to an overloading of the inoculum dose since doses ranging from 3 x 10(4) to 3 x 10(7) MLM did not produce any granulomatous local reaction as in C57Bl/6 mice. The injection of dead bacilli in the contralateral footpad of subcutaneously (s.c.) infected C3H mice revealed Arthus-like and 18--24 hr delayed reactions. When 10(6) L.MLM per mouse were injected intravenously (i.v.), systemic infection, measured in the spleen, was found to be less restricted in C57Bl/6 than in C3H mice. Moreover, in C57Bl/6 mice low doses of L.MLM injected i.v. delayed the local reaction at first, then enhanced footpad swelling and AFB counts in the draining nodes, indicating some acquired defect of peripheral immunity. When a high dose of L.MLM (2 x 10(8)/mouse) was injected i.v., C57Bl/6 mice died sooner than C3H mice, indicating certain discrepancies between local resistance and systemic susceptibility.     

Role of natural killer cells in infection with the mouse pneumonitis agent (murine Chlamydia trachomatis).

Natural killer (NK) activity is increased in both spleen and lung early in pulmonary infection by murine Chlamydia trachomatis in both susceptible nude and resistant heterozygous (nu/+) mice. Ablation of the rise in NK activity by giving the mice antiasialo GM-1 antibody or stimulation of NK activity by immunomodulators did not affect quantitative tissue counts of the mouse pneumonitis biovar of C. trachomatis or significantly affect survival. Studies are needed to further define the role of NK cells in host defense, immunoregulation, and immunopathology during chlamydial infection.     

C57Bl/6 mice are more resistant to hypoxic hypoxia than BALB/c mice

C57B1/6 mice with low intensity of metabolic processes are more resistant to hypoxic hypoxia than BALB/c mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 511–513, November, 1999     

Determination of oxidation phenotype in inbred C57Bl/6 and BALB/C mice

Research Laboratory of Pharmacogenetics, aand Research Laboratory of Pharmacokinetics, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 11, pp. 491–493, November, 1990.     

Inhibition of apoptosis by gamma interferon in cells and mice infected with Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis)

The effect of gamma interferon (IFN-gamma) on apoptosis due to infection by Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN-gamma concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due to C. muridarum infection. In cells treated with an IFN-gamma concentration that leads to the development of a heterogenous population of normal and aberrant Chlamydia vacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN-gamma appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected with C. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN-gamma-deficient mice. These results suggest that IFN-gamma may contribute to pathogenesis of persistent Chlamydia infections in vivo by preventing apoptosis of infected cells.     

Variants of secondary immune response in CBA and C57Bl/6 mice

The manifestation of a secondary immune response to intraperitoneal and subcutaneous injection of sheep red cells in various doses was studied in CBA and C57Bl/6 mice. The parameters under study were the delayed-type hypersensitivity reaction and antibody production assessed from the levels of antibody-producing cells of classes M and G in the lymph node and spleen. The manifestation and correlations between delayed-type hypersensitivity and antibody production were found to depend on the route of antigen administration and its first immunizing dose, interval between the two immunizations, and genetic control of the immune response. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 486–488, November, 1994 Presented by K. P. Kashkin, Member of the Russian Academy of Medical Sciences     

Host resistance to primary and secondary Campylobacter jejuni infections in C57Bl/6 mice

Campylobacter jejuni has been known as a main causative agent of human enterocolitis for more than 30 years. This has prompted the research on defence mechanisms of the host involved. Although the humoral immune response to C. jejuni has been addressed in many studies, relatively little is known about the role of T lymphocytes in campylobacteriosis. The current study was based on in vivo T-cell subsets depletion to evaluate the role of CD4+ and CD8+ T lymphocytes in disseminated C. jejuni infection in C57BL/6 mice. Depletion of either CD8+ or CD4+ cells did not change the overall infection kinetics of primary campylobacteriosis. To assess the role of T cells in acquired immunity that develops during primary infection in C57BL/6 mice, in vivo depletions were performed during reinfection. Depletion of CD4+ cells did not have any effect on secondary infection kinetics, whereas depletion of CD8+ cells resulted in secondary liver infection that failed to resolve during the observed period. This study showed that both CD8+ and CD4+ T cells contribute to protection of C57BL/6 mice against C. jejuni. However, the predominant role resides in the CD8+ cell subpopulation. The exact mechanisms by which CD8+ cells operate during the course of campylobacteriosis will be the subject of our further research.     

Sensitivity of immunocompetent cells of DBA/2 and C57Bl/6 mice to cyclophosphamide

T cells were most sensitive to cyclophosphamide in DBA/2 mice, while in C57Bl/6 mice both T and B cells were sensitive. The formation of antibody-producing cells and the production of specific antibodies were delayed in DBA/2 mice immunized after pretreatment with antitumor drug. Accumulation of antibody-producing cells in the spleen was more active in immunized C57Bl/6 mice treated with cyclophosphamide compared to animals not treated with cyclophosphamide.     

Immunoprophylaxis of Chlamydia trachomatis lymphogranuloma venereum pneumonitis in mice by oral immunization.

Groups of BALB/c mice were orally immunized with chlamydiae and challenged intranasally to determine whether oral immunization offers protection against pulmonary disease and to characterize the nature and kinetics of the chlamydial antibody response in the lung and other mucosal sites. Protection by oral immunization from chlamydial lung disease was demonstrated by lack of replication of the organism and the lack of chlamydial antigen in lung tissue. The chlamydial immunoglobulin A (IgA) antibody response was present at all body sites, reaching peak levels in the lung as well as in the serum. Classical IgA booster effect kinetics was observed after intranasal challenge, especially in the lung. Specific IgG antibody was detected at all body sites but at lower levels. Furthermore, animals immunized orally had no pneumonic process, as determined by histopathology. These studies also suggest that passively acquired specific serum IgG antibody may not significantly influence the course of mucosal replication of the organism. These observations indicate that oral immunization activating the gut-associated lymphoid tissue system gave total protection against chlamydial lung disease, suggesting migration of immunologically competent cells from the intestine to the lung.     

Intranasal inoculation of Chlamydia trachomatis mouse pneumonitis agent induces significant neutrophil infiltration which is not efficient in controlling the infection in mice

Previous studies have shown that chlamydial infection is accompanied by significant infiltration of neutrophils at the site of infection. However, the role of neutrophils in host defence against chlamydial infection is not clearly understood. Using genetically different inbred mouse strains and CXCR-2 gene knockout (KO) mice, we examined the mechanism for neutrophil recruitment and the role of neutrophils during chlamydial lung infection. Our data showed that C3H mice exhibited significantly higher and more persistent neutrophil infiltration in the lung than did C57BL/6 mice following Chlamydia trachomatis mouse pneumonitis infection. The massive neutrophil infiltration in C3H mice was paralleled by high-level expression of CXCR-2 and its ligands, CXC chemokines (macrophage inflammatory protein 2, cytokine-induced neutrophil attractant (KC) and lipopolysaccharide-induced CXC chemokine), and proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-1 and interleukin-6) in the lung. Although much greater infiltration of neutrophils was observed in C3H mice than in C57BL/6 mice, the former mice had more severe disease and higher in vivo chlamydial growth than the latter. Moreover, CXCR-2 KO mice, which revealed a dramatic reduction in neutrophil activity, showed comparable chlamydial infection to wild-type mice. These results suggest that neutrophils are not efficient for controlling chlamydial lung infection.     

Effects of zoosocial conflict on immunological reactivity of C57Bl/6 mice

In aggressive C57Bl/6 mice, the immune response is shown to be enhanced after 20 confrontations with submissive mice. In submissive mice, the response is inhibited after 10–20 confrontations with aggressive partners. It is concluded that stimulation and inhibition of the immune response are associated with the formation of a neurochemical set which is dopaminergic in aggressive mice and serotoninergic in submissive ones. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, No. 11, pp. 541–543, November, 1996     

Effect of hyperlipidemia on thymocyte sensitivity to apoptosis in CBA and C57Bl/6 mice

Effects of experimental hyperlipidemia on apoptosis and proliferation of thymocytes in response to mitogens were studied in CBA and C57Bl/6 mice. The concentrations of cholesterol in the serum and thymocyte membranes increased in both mouse strains. Spontaneous and dexamethasone-induced apoptosisin vitro and the proliferative response to phytohemagglutinin and concanavalin A were enhanced in thymocytes from C57Bl/6 mice and suppressed in cells from CBA mice. These data suggest opposite reactions of thymocyte to increased serum cholesterol concentration in these two strains, associated with stimulation and suppression of cell activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 200–202, August, 2000     

Analysis of the immune response in mice following intrauterine infection with the Chlamydia trachomatis mouse pneumonitis biovar.

A Swiss Webster white mouse model of salpingitis was used to characterize the immune response following an intrauterine infection with the Chlamydia trachomatis mouse pneumonitis biovar. Western blot (immunoblot) analyses of the serum samples showed that the immunodominant bands corresponded to molecular masses of 72, 60, 42, and 28 kDa and to the lipopolysaccharide. Antibodies to the 60-kDa heat shock protein and to the 60-kDa cysteine-rich protein were detected at 2 and 3 weeks postinfection, respectively. Neutralization was observed in an in vitro assay with serum samples as early as the 3rd day postinfection and remained high for the 7 weeks of observation. The mice were mated in the 7th week following infection. Of the infected experimental mice, 71.4% were found to be either unilaterally or bilaterally infertile, whereas only 27.4% of the noninfected control mice were found to be infertile.     

Influenza virus host response of C57Bl/6 mice treated with TACI-Ig

TACI-Ig is a soluble glycoprotein comprised of a human IgG₁-Fc fused with the extracellular domain of the human TACI receptor. Chronic exposure to TACI-Ig is associated with reduced circulating B cells in mouse and non-human primates, and a concomitant decrease in circulating immunoglobulin. Because of these activities, TACI-Ig is in clinical evaluation for treatment of various autoimmune diseases and B cell malignancies. In this study, the effect of TACI-Ig treatment on the ability of C57Bl/6 mice to clear influenza virus was evaluated. C57Bl/6 mice were exposed to vehicle (negative control), dexamethasone (positive control), or TACI-Ig (0.05, 0.50, or 5.0 mg/kg, SC, thrice weekly) from within one week prior to viral exposure through 21 days thereafter. Dexamethasone treatment of influenza-infected mice prolonged the infection, and decreased survival, body weight, lymphoid organ weight, influenza-specific IgM and IgG, and viral clearance relative to control animals, consistent with its expected immunosuppressive activity. Animals treated with TACI-Ig (0.05, 0.50, and 5.0 mg/kg) demonstrated a dose-dependent decrease in spleen weight and influenza-specific IgG and IgM in both lung and serum relative to control animals. In addition, flow cytometric analyses showed a decrease in B cells, but not T cells, in peripheral blood in animals treated with TACI-Ig. However, neither viral clearance nor survival was affected by TACI-Ig treatment. These data demonstrate the expected B cell-specific pharmacological effects of TACI-Ig in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance. It is concluded that non-B cell related antiviral competence remains intact during TACI-Ig treatment.     

Age- and gender-specific changes of hypocretin immunopositive neurons in C57Bl/6 mice

Loss of neurons or neuronal functions over time has been hypothesized to contribute to the dysregulation of autonomic functions observed in aging. In this study, we evaluated the total number of the hypothalamic hypocretin (orexin) immunopositive neurons in 100, 400, 800 and 1000-day-old male and female C57Bl/6 mice that are commonly used in aging studies in vertebrates. Males had 15–20% more hypocretin immunopositive neurons (HIN) than females at all ages examined. Neuronal number for both sexes was stable in the first 400 days of life, but started declining between 400 and 800 days with rates of approximately 1 neuron/day. The rate of loss doubled in males between 800 and 1000 days of age. The total average number of HIN for males was 2251 ± 139 at 100 days, 2235 ± 112 at 400 days, 1914 ± 81 at 800 days, and 1596 ± 301 at 1000 days. The total average number of HIN for females was 1805 ± 76 at 100 days, 1887 ± 118 at 400 days, and 1521 ± 181 at 800 days. Evaluation of the time-dependent decline in the number of hypocretin immunopositive neurons may help to explain the physiological changes in sleep or energy homeostasis regulation during aging.     

Antioxidant enzymes and lipid peroxidation in C57Bl/6 and BALB/c mice

Superoxide dismutase and catalase activities and levels of thiobarbituric acid-reactive lipid peroxidation (LPO) products were estimated in the liver of C57B1/6 and BALB/c mice. The results indicate that although antioxidant enzymes are more active in BALB/c mice, compensation of oxidation processes in this strain is possible only if LPO-inducing agents are absent or present at low levels, and that these agents, including exogenous ones, may be expected to activate lipid oxidation in this strain to a greater extent than in C57Bl/6 mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 580–583, December, 1995