Chlamydia pneumoniae infection in IL-10 knock out mice: Accelerated clearance but severe pulmonary inflammatory response

Penttilä, Tuula; Haveri, Anu; Tammiruusu, Anne; Vuola, Jenni M.; Lahesmaa, Riitta; Puolakkainen, Mirja

doi:10.1016/j.micpath.2008.02.004

Cited by 21 publications

(16 citation statements)

References 11 publications

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“…It has been reported that endogenously produced IL-10 differentially regulates chlamydial infections among inbred mouse strains [23]. For example, using the murine model of C. trachomatis MoPn lung infection, IL-10 inhibits host clearance of chlamydial infection in the susceptible BALB/C mouse strain (which produces more IL-10) and negatively regulates inflammatory responses in the resistant C57BL/6 mouse (which produces less IL-10) [23].…”

Section: Discussionmentioning

confidence: 99%

“…For example, using the murine model of C. trachomatis MoPn lung infection, IL-10 inhibits host clearance of chlamydial infection in the susceptible BALB/C mouse strain (which produces more IL-10) and negatively regulates inflammatory responses in the resistant C57BL/6 mouse (which produces less IL-10) [23]. Using primed spleen cells, Yang et al [20] have shown further that the levels of IFN- γ , TNF, and IL-12 were decreased when exogenous IL-10 was added to Chlamydia- infected C57BL/6 IL-10 knockout mice, indicating that IL-10 reduces the levels of cytokines produced during the infection process in the lung model.…”

Section: Discussionmentioning

confidence: 99%

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The Anti-Inflammatory Cytokine, Interleukin-10, Inhibits Inflammatory Mediators in Human Epithelial Cells and Mouse Macrophages Exposed to Live and UV-InactivatedChlamydia trachomatis

Yilma

Singh

Fairley

et al. 2012

Mediators of Inflammation

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Chlamydia trachomatisinfects macrophages and epithelial cells evoking acute and chronic inflammatory conditions, which, if not controlled, may put patients at risk for major health issues such as pelvic inflammatory disease, chronic abdominal pain, and infertility. Here we hypothesized that IL-10, with anti-inflammatory properties, will inhibit inflammatory mediators that are produced by innate immune cells exposed toC. trachomatis. We used human epithelial (HeLa) cells and mouse J774 macrophages as target cells along with live and UV-inactivatedC. trachomatismouse pneumonitis (MoPn) as stimulants. Confocal microscopy employing an anti-Chlamydiaantibody confirmed cells infectivity by day 1, which persisted up to day 3. Kinetics studies revealed that liveC. trachomatisinduced TNF, IL-6, and IL-8, as a function of time, with day-2 infection inducing the highest cytokine levels. Exogenous IL-10 inhibited TNF, IL-6, and IL-8 as secreted by day-2 infected cells. Similarly, IL-10 diminished cytokine levels as produced by macrophages exposed to UV-inactivatedChlamydia, suggesting the IL-10-mediated inhibition of cytokines is not restricted to live organisms. Our data imply that IL-10 is an important regulator of the initial inflammatory response toC. trachomatisinfection and that further investigations be made into IL-10 use to combat inflammation induced by this bacterium.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Cytokine, Interleukin-10, Inhibits Inflammatory Mediators in Human Epithelial Cells and Mouse Macrophages Exposed to Live and UV-InactivatedChlamydia trachomatis

Yilma

Singh

Fairley

et al. 2012

Mediators of Inflammation

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“…During the preparation of this manuscript, two studies were published that examined the role of other endogenous regulators of innate immunity in C. pneumoniae infection. In the absence of the immunosuppressive cytokine IL-10, chlamydial infection triggered more severe inflammation, which was associated with accelerated clearance of the bacterium [31]. Dusp1 expression is induced by IL-10 [32] and probably mediates part of its effects.…”

Section: Discussionmentioning

confidence: 99%

Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1-/- mice: critical role of IL-6

Rodríguez

Dietrich

Moßbrugger

et al. 2010

Journal of Leukocyte Biology

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The MAPK phosphatase DUSP1 is an essential negative regulator of TLR-triggered innate immune activation. Here, we have investigated the impact of DUSP1 on inflammatory and antimicrobial host responses to the intracellular pathogen Chlamydophila pneumoniae. Following nasal infection, DUSP1-deficient mice mounted an enhanced pulmonary cytokine (IL-1beta, IL-6) and chemokine response (CCL3, CCL4, CXCL1, CXCL2), leading to increased leukocyte infiltration. Of interest, the increased inflammatory response, in the absence of DUSP1, was associated with higher bacterial numbers in the lungs, although the expression of IFN-gamma and critical antichlamydial effector molecules, such as iNOS, was intact. Blockade of IL-6 trans-signaling by injection of a soluble gp130-Fc fusion protein corrected the overshooting chemokine production as well as the increased chlamydial load in Dusp1(-/-) mice. Furthermore, IL-6 enhanced the replication of C. pneumoniae in embryonic fibroblasts in vitro. These data show that DUSP1 is required to achieve a balanced response to chlamydial infection and identify IL-6 as critical for amplifying inflammation and benefiting chlamydial growth through direct effects on infected cells.

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“…Mouse models have demonstrated that IFN-␤ and IL-1␣ contribute to the pulmonary inflammatory response to C. pneumoniae infection (28,39). The findings of this study suggest that these cytokines impair the capacity of fibroblasts to synthesize interstitial collagens and fibronectin.…”

Section: Discussionmentioning

confidence: 62%

Host Cell Cytokines Induced by Chlamydia pneumoniae Decrease the Expression of Interstitial Collagens and Fibronectin in Fibroblasts

Baumert¹,

Schmidt²,

Eitner

et al. 2009

Infect Immun

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Chlamydia pneumoniae infection has been associated with chronic obstructive airway disease (COPD), asthma, and atherosclerosis. Inflammation and airway remodeling in asthma and COPD result in subepithelial fibrosis that is characterized by the deposition of interstitial collagens and fibronectin. The progression of atherosclerosis is also accompanied by an increased production of interstitial collagens in the intima. As shown by reverse transcription-PCR and immunoblotting, infection of human fibroblasts and smooth muscle cells by C. pneumoniae TW-183 downregulated the expression of type I and III collagen and fibronectin, whereas the level of type IV collagen remained unchanged. Conditioned medium from infected fibroblasts as well as epithelial WISH cells also reduced the expression of interstitial collagens and fibronectin in uninfected cells. In experiments using blocking antibodies, beta interferon was found to contribute to the inhibitory effects of conditioned medium collected from infected fibroblasts. In contrast, downregulation of matrix protein expression by conditioned medium from epithelial cells was caused by interleukin-1␣, which was not secreted from fibroblasts following chlamydial infection. C. pneumoniae-mediated inhibition of collagen and fibronectin expression was diminished following transfection of fibroblasts with specific small interfering RNA targeting the transcription factor CCAAT/enhancer-binding protein ␤. The downregulation of interstitial collagens and fibronectin by the Chlamydia-induced host cell cytokine response may modulate tissue remodeling processes in airway diseases. In atherosclerosis the inhibition of collagen synthesis by C. pneumoniae infection may promote plaque vulnerability, thereby increasing the risk of plaque rupture.

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Chlamydia pneumoniae infection in IL-10 knock out mice: Accelerated clearance but severe pulmonary inflammatory response

Cited by 21 publications

References 11 publications

The Anti-Inflammatory Cytokine, Interleukin-10, Inhibits Inflammatory Mediators in Human Epithelial Cells and Mouse Macrophages Exposed to Live and UV-InactivatedChlamydia trachomatis

The Anti-Inflammatory Cytokine, Interleukin-10, Inhibits Inflammatory Mediators in Human Epithelial Cells and Mouse Macrophages Exposed to Live and UV-InactivatedChlamydia trachomatis

Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1-/- mice: critical role of IL-6

Host Cell Cytokines Induced by Chlamydia pneumoniae Decrease the Expression of Interstitial Collagens and Fibronectin in Fibroblasts

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