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Chlamydia pneumoniae infection of the central nervous system worsens experimental allergic encephalitis.

Du C, Yao SY, Ljunggren-Rose A, Sriram S - J. Exp. Med. (2002)

Bottom Line: Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis.Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS.These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

ABSTRACT
Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis. Intraperitoneal inoculation of mice with Chlamydia pneumoniae, after immunization with neural antigens, increased the severity of EAE. Accentuation of EAE required live infectious C. pneumoniae, and the severity of the disease was attenuated with antiinfective therapy. After immunization with neural antigens, systemic infection with C. pneumoniae led to the dissemination of the organism into the central nervous system (CNS) in mice with accentuated EAE. Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS. These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE. We propose that infection of the CNS by C. pneumoniae can amplify the autoreactive pool of lymphocytes and regulate the expression of an autoimmune disease.

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Effect of infection C. pneumoniae and C. trachomatis on the development of an immune response to MBP. SJL/J female mice were immunized with MBP and infected with chlamydial organisms as described in Fig. 1 A. (Top) Proliferative response of splenocytes to MBP in infected and uninfected mice. The data represents the mean value and SD (standard deviation) of [3H]thymidine uptake (CPM) of triplicate determination at each point. (Bottom) IFN-γ production in culture supernatants in response to MBP. The levels of IFN-γ in supernatants were measured by ELISA at 48 and 72 h, respectively. The data represents the mean and standard value (SD) of triplicate determinations at each time point from a representative three experiments (CT, C. trachomatis; CP, C. pneumoniae).
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fig5: Effect of infection C. pneumoniae and C. trachomatis on the development of an immune response to MBP. SJL/J female mice were immunized with MBP and infected with chlamydial organisms as described in Fig. 1 A. (Top) Proliferative response of splenocytes to MBP in infected and uninfected mice. The data represents the mean value and SD (standard deviation) of [3H]thymidine uptake (CPM) of triplicate determination at each point. (Bottom) IFN-γ production in culture supernatants in response to MBP. The levels of IFN-γ in supernatants were measured by ELISA at 48 and 72 h, respectively. The data represents the mean and standard value (SD) of triplicate determinations at each time point from a representative three experiments (CT, C. trachomatis; CP, C. pneumoniae).

Mentions: We next examined if worsening of EAE in mice inoculated with C. pneumoniae was due to an increase in activation of MBP reactive Th1 cells. We determined the effect of in vivo infection with live chlamydia on lymphocyte proliferation and IFN-γ production to MBP in, in vitro cultures. Proliferation counts to MBP, obtained from mice immunized with MBP and infected with C. pneumoniae increased from background levels of 4,305 ± 120 to 28,854 ± 1,154 cpm to in the presence of 50 μg/ml of MBP. Background counts in C. trachomatis mice was 4,196 ± 1,492 cpm, which increased to 19,308 ± 932 cpm in the presence of MBP. In uninfected mice, proliferative response to MBP increased from 3,916 ± 186 to 15,068 ± 815, in the presence of MBP. The proliferative response to MBP was higher in both C. pneumoniae and C. trachomatis infected mice when compared with uninfected controls suggesting that concurrent infection with chlamydia can amplify an autoimmune response. A proliferative response to MBP was not seen in mice infected with C. pneumoniae alone, suggesting a lack of cross reactivity between C. pneumoniae antigens and MBP (Fig. 5) . IFN-γ levels in lymphocyte culture supernatants were similarly higher in C. pneumoniae (1,020 pg/ml) and C. trachomatis infected mice (950 pg/ml) when compared with uninfected mice (612 pg/ml; P < 0.05, Fig. 5). These observations suggest that unlike its different effects on paralytic EAE, both C. trachomatis and C. pneumoniae infections are capable of enhancing T cell proliferation and IFN-γ production in response to MBP over that seen in uninfected controls.


Chlamydia pneumoniae infection of the central nervous system worsens experimental allergic encephalitis.

Du C, Yao SY, Ljunggren-Rose A, Sriram S - J. Exp. Med. (2002)

Effect of infection C. pneumoniae and C. trachomatis on the development of an immune response to MBP. SJL/J female mice were immunized with MBP and infected with chlamydial organisms as described in Fig. 1 A. (Top) Proliferative response of splenocytes to MBP in infected and uninfected mice. The data represents the mean value and SD (standard deviation) of [3H]thymidine uptake (CPM) of triplicate determination at each point. (Bottom) IFN-γ production in culture supernatants in response to MBP. The levels of IFN-γ in supernatants were measured by ELISA at 48 and 72 h, respectively. The data represents the mean and standard value (SD) of triplicate determinations at each time point from a representative three experiments (CT, C. trachomatis; CP, C. pneumoniae).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196067&req=5

fig5: Effect of infection C. pneumoniae and C. trachomatis on the development of an immune response to MBP. SJL/J female mice were immunized with MBP and infected with chlamydial organisms as described in Fig. 1 A. (Top) Proliferative response of splenocytes to MBP in infected and uninfected mice. The data represents the mean value and SD (standard deviation) of [3H]thymidine uptake (CPM) of triplicate determination at each point. (Bottom) IFN-γ production in culture supernatants in response to MBP. The levels of IFN-γ in supernatants were measured by ELISA at 48 and 72 h, respectively. The data represents the mean and standard value (SD) of triplicate determinations at each time point from a representative three experiments (CT, C. trachomatis; CP, C. pneumoniae).
Mentions: We next examined if worsening of EAE in mice inoculated with C. pneumoniae was due to an increase in activation of MBP reactive Th1 cells. We determined the effect of in vivo infection with live chlamydia on lymphocyte proliferation and IFN-γ production to MBP in, in vitro cultures. Proliferation counts to MBP, obtained from mice immunized with MBP and infected with C. pneumoniae increased from background levels of 4,305 ± 120 to 28,854 ± 1,154 cpm to in the presence of 50 μg/ml of MBP. Background counts in C. trachomatis mice was 4,196 ± 1,492 cpm, which increased to 19,308 ± 932 cpm in the presence of MBP. In uninfected mice, proliferative response to MBP increased from 3,916 ± 186 to 15,068 ± 815, in the presence of MBP. The proliferative response to MBP was higher in both C. pneumoniae and C. trachomatis infected mice when compared with uninfected controls suggesting that concurrent infection with chlamydia can amplify an autoimmune response. A proliferative response to MBP was not seen in mice infected with C. pneumoniae alone, suggesting a lack of cross reactivity between C. pneumoniae antigens and MBP (Fig. 5) . IFN-γ levels in lymphocyte culture supernatants were similarly higher in C. pneumoniae (1,020 pg/ml) and C. trachomatis infected mice (950 pg/ml) when compared with uninfected mice (612 pg/ml; P < 0.05, Fig. 5). These observations suggest that unlike its different effects on paralytic EAE, both C. trachomatis and C. pneumoniae infections are capable of enhancing T cell proliferation and IFN-γ production in response to MBP over that seen in uninfected controls.

Bottom Line: Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis.Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS.These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

ABSTRACT
Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis. Intraperitoneal inoculation of mice with Chlamydia pneumoniae, after immunization with neural antigens, increased the severity of EAE. Accentuation of EAE required live infectious C. pneumoniae, and the severity of the disease was attenuated with antiinfective therapy. After immunization with neural antigens, systemic infection with C. pneumoniae led to the dissemination of the organism into the central nervous system (CNS) in mice with accentuated EAE. Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS. These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE. We propose that infection of the CNS by C. pneumoniae can amplify the autoreactive pool of lymphocytes and regulate the expression of an autoimmune disease.

Show MeSH
Related in: MedlinePlus