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1.
McCaskill JG Chason KD Hua X Neuringer IP Ghio AJ Funkhouser WK Tilley SL 《American journal of respiratory cell and molecular biology》2006,35(3):347-356
Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung. 相似文献
2.
Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β2-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes. 相似文献
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Eduardo Martins de Sousa Fernando Bonfim de Bortoli Eduardo Pinheiro Amaral Aline Carvalho Batista Thereza Liberman Kipnis Alessandra Marques Cardoso André Kipnis Ana Paula Junqueira-Kipnis 《Infection and immunity》2010,78(4):1571-1581
Mycobacterium massiliense is an environmental opportunistic pathogen that has been associated with soft tissue infection after minor surgery. We studied the acute immune response of C57BL/6 and BALB/c mice infected intravenously with 106 CFU of an M. massiliense strain isolated from a nosocomial infection in Brazil. The results presented here show that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells, and natural killer cells induced by gamma interferon and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.Mycobacteria that do not belong to the complex Mycobacterium tuberculosis are known as nontuberculous mycobacteria (NTM) or atypical mycobacteria. NTM are ubiquitous microorganisms found worldwide in soil and water (3, 23, 38). These environmental mycobacteria are considered emerging and environmental opportunistic pathogens (6, 23).Mycobacterium massiliense is an environmental nonphotochromogenic, rapidly growing Mycobacterium strain that has been associated with soft-tissue infection after minor surgery or intramuscular injection (3, 5, 17, 22, 26, 46) and with pulmonary infection due to diseases, such as cystic fibrosis (29, 41). This species differs only slightly from Mycobacterium abscessus, sharing a 99.6% sequence identity of their 16S rRNA genes; genetic differences can be observed by comparative sequence analysis of the rpoB and hsp65 genes (1, 25, 42). Infections with these agents tend to respond poorly to macrolide-based chemotherapy (3), even though the organisms are susceptible to clarithromycin (15, 44, 47).M. massiliense infection mainly affects immunocompetent individuals and occasionally is associated with disseminated disease (8). An outbreak of M. massiliense occurred in Goiania, Brazil, where 30 individuals were infected after undergoing knee joint and laparoscopic surgery (5). Despite the fact that the infected individuals were from different hospitals, a unique M. massiliense strain was identified and characterized by pulsed-field gel electrophoresis.Disease pathogenesis involves host-pathogen interactions that directly affect parasite clearance. Typically, when environmental bacteria are passively introduced into the host, rapid bacterial clearance occurs due to an efficient innate immune response (30). Nonetheless, accidental infections with M. massiliense have been described as having a chronic evolution and, in some cases, the disease is disseminated irrespective of the host''s immune status. Such findings raise the possibility that this species is more virulent and/or pathogenic than other environmental mycobacteria, such as M. chelonae and M. abscessus.Recently, a murine model of M. abscessus infection was described, and isogenic mice were shown to be good models to address the immune response of the host (34, 39). In the present study, we analyzed the immune response of C57BL/6 and BALB/c mice infected with a clinical isolate of M. massiliense obtained from the recent outbreak in Goiania, Brazil. We show here that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells (DCs), and natural killer (NK) cells induced mainly by gamma interferon (IFN-γ) and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice. 相似文献
5.
Antibody and cytokine responses to the cilium-associated respiratory bacillus in BALB/c and C57BL/6 mice
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Kendall LV Riley LK Hook RR Besch-Williford CL Franklin CL 《Infection and immunity》2000,68(9):4961-4967
The cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding bacterium that causes persistent respiratory tract infections in rodents despite histologic and serologic evidence of a marked immune response. To assess humoral immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c and C57BL/6 mice were inoculated intratracheally with 10(5) CAR bacillus organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM], IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], and interleukin-4 [IL-4]) were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days. BALB/c mice developed CAR bacillus-induced lesions early in the course of disease that became more severe with time. Correlating with increasing disease severity, BALB/c mice had elevations in all antibody isotypes tested, and elevations in pulmonary TNF-alpha, IFN-gamma, and IL-4. C57BL/6 mice developed mild lesions with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6 mice. The persistence of infection in BALB/c mice with vigorous serum antibody responses and increased IFN-gamma and IL-4 responses suggests that humoral immunity and T-cell responses are ineffective at preventing CAR bacillus disease. Furthermore, the lackluster antibody responses and undetectable cytokine responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are not critical in resistance to CAR bacillus-induced disease. 相似文献
6.
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 相似文献
7.
Yersinia enterocolitica infection in resistant and susceptible strains of mice. 总被引:2,自引:8,他引:2
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We investigated natural resistance in mice to Yersinia enterocolitica, an enteric bacterial pathogen of humans, with a view to determine host genetic factors that are important in resistance. Most mouse strains studied (C3H/HeN, BALB/c, BALB.B, DBA/2, A, Swiss, and SWR) were highly susceptible to infection (50% lethal dose [LD50], 2 X 10(2) to 6 X 10(2) Y. enterocolitica administered intravenously [i.v.]). In contrast, C57BL/6 mice were highly resistant (LD50, 2 X 10(5) Y. enterocolitica administered i.v.). Resistance to i.v. Yersinia infection did not appear to be related to the Ity locus (which codes for resistance to Salmonella typhimurium and other pathogens) because Ityr mice (C3H/HeN, DBA/2, A, and SWR) were more susceptible to Y. enterocolitica than were Itys (C57BL/6) mice. In addition, because BALB.B mice (congenic to C57BL/6 mice at the H-2 locus) were susceptible, resistance was probably not H-2 linked. BALB/c X C57BL/6 F1 mice were intermediate in their resistance to Y. enterocolitica infection (LD50, 3 X 10(4) organisms administered i.v.), suggesting that resistance to Y. enterocolitica depends on a gene dosage affect or a resistance gene(s) interaction between susceptible and resistant parents. Further studies with C57BL/6 and BALB/c mice as prototype resistant and susceptible strains were undertaken. A time course study of Y. enterocolitica growth in various organs following i.v. infection revealed no strain difference in bacterial growth during the first 48 h of infection. Thereafter, however, C57BL/6 mice were capable of restricting Y. enterocolitica growth in all tissues (liver, lung, spleen, kidneys), whereas extensive bacterial proliferation occurred in BALB/c mice tissues. BALB/c mice were also more susceptible to oral Y. enterocolitica infection than were C57BL/6 mice, demonstrating increased mortality and greater numbers of bacteria in the Peyer's patches. Finally, whereas thymus-bearing C57BL/6 X BALB/c F1 mice were resistant to infection, athymic (nude) C57BL/6 X BALB/c F1 mice were susceptible. These studies provide a model to investigate natural immunity to enteric pathogens at mucosal surfaces, as well as provide the basis for clarifying the role of host genotype in Y. enterocolitica resistance. 相似文献
8.
Inflammatory response differences between C57BL/6 and BALB/c mice following ovalbumin (OVA) sensitization and a single challenge were investigated. Serum immunoglobulin (Ig)E and IgG1 levels were higher in C57BL/6 mice than in BALB/c mice. In contrast, IgG2a levels in C57BL/6 mice were lower than in BALB/c mice. Furthermore, the number of eosinophils infiltrating into lungs in C57BL/6 mice was significantly higher than in BALB/c mice after OVA challenge. The levels of the T helper 2 (Th2)-type cytokines interleukin (IL)-4 and IL-5, generated in challenged C57BL/6 lung tissue, were also higher than in BALB/c lung tissue. The participation of IL-4 and IL-5 in the induction of eosinophil infiltration into the lungs was confirmed in both strains of mice by injection of anti-IL-4 and anti-IL-5 monoclonal antibodies (mAbs). However, following OVA stimulation, in vitro IL-4 and IL-5 production in splenocyte cultures from C57BL/6 mice was lower than in splenocyte cultures from BALB/c mice. These results indicate that C57BL/6 mice induce Th2-type responses in the lungs, while BALB/c mice induce T helper 1 (Th1)-type responses in the lungs, despite considerable production of IL-4 and IL-5 from splenocytes. Therefore, local immune responses are more important in the induction of allergic inflammation in the lungs and are different from systemic immune responses, which are thought to depend on genetic background. 相似文献
9.
Differences in resistance of C57BL/6 and C57BL/10 mice to infection by Mycobacterium avium are independent of gamma interferon
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After infection with a low-virulence strain of Mycobacterium avium, C57BL/6 and C57BL/10 mice had clear differences in the control of the infection in their livers and spleens. This difference in susceptibility was not associated with differences in the H-2 complex. It was dependent on the activity of CD4(+) T cells but unrelated to the ability of these cells to secrete gamma interferon or to the development of delayed-type hypersensitivity responses at 3 weeks of infection. It was associated with lower total numbers of CD4(+) cells present in infected spleens and was related to an earlier induction of protective T cells, as measured by adoptive-transfer assays. These data further strengthen the notion of gamma-interferon-independent mechanisms of protection against mycobacteria. 相似文献
10.
Trunova GV Makarova OV Diatroptov ME Bogdanova IM Mikchailova LP Abdulaeva SO 《Bulletin of experimental biology and medicine》2011,151(1):99-102
Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological
processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and
functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice,
volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6
mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic
activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of
adaptive processes and different sensitivity of these mice to pathogenic agents. 相似文献
11.
Huaiyong Chen Dongmei Liao Derek Cain Ian McLeod Yoshihiro Ueda Ziqiang Guan Christian Raetz Garnett Kelsoe 《International journal of experimental pathology》2010,91(5):460-471
Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in the C57BL/6J and BALB/cByJ strains of mice. The formation and kinetics of oil granulomas were distinct between the two strains. In C57BL/6J mice, injected pristane induced oil granuloma formation at both the mesenteric centers (MG) and margins (SG). MG was resolving by 11 weeks, and SG persisted. In BALB/cByJ mice, MG developed slower but persisted longer than in C57BL/6J mice, and SG resolved sooner than in C57BL/6J mice. Injection of India ink revealed that phagocytes were localised mainly to the SG in C57BL/6J mice, but were located diffusely in both MG and SG of BALB/cByJ mice. SG cells expressed more monocyte chemotactic protein‐1 (MCP‐1) mRNA than MG cells in C57BL/6J mice, but there was no difference in MCP‐1 expression between the MG and SG in BALB/cByJ mice. These observations suggest that the recruitment of inflammatory leucocytes under the direction of chemokines differentiates the patterns of granuloma responses to pristane in C57BL/6J and BALB/cByJ mice. 相似文献
12.
Hayashi T Hasegawa K Nakai S Hamachi T Adachi Y Yamauchi Y Maeda K 《Journal of comparative pathology》2001,125(2-3):208-213
In this study, histopathological bronchial-bronchiolar lesions of the late asthmatic responses induced by ovalbumin in BALB/c and C57BL/6 mice were compared. Prominent goblet cell hyperplasia and metaplasia with mucous secretion, and desquamation of epithelial cells with severe infiltration of eosinophils and lymphocytes, were observed in the BALB/c mice; in the C57BL/6 mice, however, these changes were less severe. The reduced histopathological changes in the C57BL/6 mice were associated with a decreased infiltrate of eosinophils, decreased serum immunoglobulin-E (IgE) concentrations and increased serum interferon-gamma concentrations. The results suggest that the reduced bronchial lesions in C57BL/6 mice were due, at least in part, to suppression of the T-helper (Th)2 immune response that underlies the decreased infiltration of lymphocytes and eosinophils into the bronchial mucosa. 相似文献
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In the present study, we used a dry maze task to assess the spatial learning ability of C57BL/6N and BALB/cA mice besides the water maze task. In Experiment 1, the performance of C57BL/6N and BALB/cA mice in the water maze task and dry maze task were investigated. In the former task, the mice had to learn the position of a hidden platform submerged below the water surface and they had to learn the position of a baited hole on the circular maze in the latter task. C57BL/6N mice showed significant learning in both maze tasks, whereas BALB/cA mice showed learning in a dry maze but not in water maze as reported before. In Experiment 2, a dry maze task was conducted on a circular open field which contained 16 holes arranged symmetrically and which was put on the same height as the surface of the water maze. In Experiment 2, BALB/cA mice showed significant improvement in latency and path length to reach the food hole. The poor performance of the BALB/cA in the water maze task may reflect a weak motivation, escaping from water, rather than the poor spatial memory in this strain. 相似文献
15.
A/J mice are susceptible and C57BL/6 mice are resistant to Listeria monocytogenes infection by intragastric inoculation 总被引:4,自引:0,他引:4
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Previous studies demonstrated that the innate resistance of mice to Listeria monocytogenes infection by intravenous or intraperitoneal inoculation is regulated principally by the Hc locus on mouse chromosome 2. The A/J and C57BL/6 mouse strains were identified as prototype L. monocytogenes-susceptible and -resistant strains, respectively. In the present study, we compared the relative susceptibilities of A/J and C57BL/6 mice to intragastric (i.g.) inoculation with L. monocytogenes. The results of our study indicate that A/J mice are significantly more susceptible than C57BL/6 mice to an i.g. challenge with L. monocytogenes. This was reflected in the estimated 50% lethal doses for the two strains (10(6) and 10(8) CFU for A/J and C57BL/6 mice, respectively) and a more rapid and severe dissemination of the infection to the spleen and liver in A/J mice than in C57BL/6 mice. Histopathological examination of tissues from the infected mice confirmed the greater severity of disease in A/J mice. Clearance of a primary infection enhanced the resistance of both A/J and C57BL/6 mice to reinfection with L. monocytogenes via the gastrointestinal tract. However, the relative difference in susceptibility between the two strains was evident even after immunization. The A/J mouse holds promise as a model for investigating the pathogenesis of gastrointestinal listeriosis because of its ability to develop systemic infection following challenge with numbers of organisms similar to those recovered from some L. monocytogenes-contaminated food products. 相似文献
16.
Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL/6 and susceptible A/J mice.
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Macrophage activation was examined in resistant C57BL/6 and susceptible A/J mice during the course of blood-stage infection with Plasmodium chabaudi AS. Three parameters of macrophage activation (lipopolysaccharide [LPS]- and malaria antigen-induced tumor necrosis factor [TNF] production in vitro, phorbol myristate acetate [PMA]-induced production of oxygen metabolites in vitro, and Ia antigen expression) were assessed during infection in populations of peritoneal and splenic macrophages recovered from infected mice of the two strains. The peak level of LPS-induced TNF production in vitro by splenic macrophages from both infected C57BL/6 and infected A/J mice occurred on day 7, which was 3 days before the peak of parasitemia. Although the kinetics of TNF production in vitro in response to either LPS, soluble malaria antigen, or intact parasitized erythrocytes varied in some of the other macrophage populations during infection, there was no significant difference in the peak level of production. Peritoneal and splenic macrophages from infected C57BL/6 mice exhibited significantly increased PMA-induced production of H2O2 in vitro on day 7. Peritoneal macrophages from infected A/J mice also exhibited significant PMA-induced H2O2 production on day 7, while production by splenic macrophages from these hosts was not increased in comparison with production by cells from normal animals. Only peritoneal macrophages from infected C57BL/6 mice produced significantly increased levels of O2-, and this occurred on day 7 postinfection. Ia antigen expression by both peritoneal and splenic macrophages from resistant C57BL/6 and susceptible A/J mice was significantly increased during P. chabaudi AS infection. However, the percentage of Ia+ peritoneal macrophages on days 8 and 10 postinfection and Ia+ splenic macrophages on day 3 postinfection was significantly higher in C57BL/6 than in A/J mice. Thus, these results demonstrate that macrophages from P. chabaudi AS-infected A/J mice exhibit defects in oxygen metabolism and Ia antigen expression which may contribute to the susceptibility of these hosts to this intraerythrocytic parasite. The cause-and-effect relationship between these defects and the susceptibility of A/J mice to P. chabaudi AS is unknown. 相似文献
17.
Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice
The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J x C57BL/6J] F(2) mice 48 h after infection with 5 x 10(4) C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-alpha levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans. 相似文献
18.
BACKGROUND: BALB/c and C57BL/6 mice are two inbred strains, but after voluntary movement, there is no report on how to scientifically reasonably select behavioral experiment methods and indicators and to evaluate the learning and memory abilities of mice. 相似文献
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Age-dependent alteration in cellular signaling is implicated in the onset of age-related hearing loss (presbycusis). The gamma subtype of protein kinase C (PKCγ) is a PKC isoenzyme exclusively expressed in central nervous system but its potential role in the presbycusis remains unclear. Using two presbycusis-like animal models (C57BL/6J strain and BALB/c strain), the auditory thresholds were assessed by auditory brainstem response (ABR) in young (2-month-old), adult (8-month-old) and old (24-month-old) groups, and the localization and expression of PKCγ in the cochlear nucleus (CN) was examined by immunohistochemistry, Western blotting and Real-Time PCR. The results showed that PKCγ immmunoreactive (-ir) neurons were mainly concentrated in the molecular layer and fusiform layer of the dorsal CN (DCN) and their number was increased significantly with aging (p<0.05). Moreover, compared with 2-month-old mice, PKCγ expression in the CN at both protein and mRNA levels was significantly increased in the 8-month-old mice and 24-month-old mice (p<0.05). Thus our findings demonstrate a potential link between the increased PKCγ expression and the age-related hearing loss in these mice, suggesting novel strategies for the prevention and therapy of age-associated auditory disorders. 相似文献