Heat shock protein 60 from <i>Chlamydia pneumoniae</i> elicits an unusual set of inflammatory responses via Toll‐like receptor 2 and 4 <i>in vivo</i>

Costa, Clarissa U. Prazeres da; Wantia, Nina; Kirschning, Carsten J.; Busch, Dirk H.; Rodríguez, Núria; Wagner, Hermann; Miethke, Thomas

doi:10.1002/eji.200425101

Cited by 94 publications

(78 citation statements)

References 30 publications

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“…The C. pneumoniae-induced NF-B activation was reduced by a blockade of the TLR4 receptor (5). Either C. pneumoniae contact or the cHSP60 induce a TLR-mediated translocation of NF-B and a secretion of cytokines (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

et al. 2006

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Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-B) is activated and tumor necrosis factor-␣ (TNF-␣) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-␣. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-␣ and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-␣ (43 Ϯ 10 versus 661 Ϯ 41 pg/mL) and MIP-2 (573 Ϯ 41 versus 4786 Ϯ 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-␣ Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IB␣ (3.7 Ϯ 0.3 versus 14 Ϯ 1) and increased NF-B p65 (31 Ϯ 7.5 versus 3.6 Ϯ 1.1) compared with control. PF5080 prevented NF-B activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 Ϯ 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 Ϯ 4% attached to and in 5 Ϯ 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade. Chlamydophila pneumoniae are obligate intracellular Gram-negative bacteria that cause respiratory infections in pediatric populations and adults (1,2). Recent studies demonstrated the presence of C. pneumoniae in alveolar macrophages and ATII cells in patients with chronic obstructive pulmonary disease (COPD) (3). Whereas most respiratory infections with C. pneumoniae are self-limited (4), bacterial colonization can lead to infectious exacerbations and development of COPD (5). Because detection rate of C. pneumonia varies significantly (6), the clinical relevance of C. pneumoniae is still controversial.The effect of C. pneumoniae on isolated ATII-cells is well characterized. C. pneumoniae inhibit the surfactant metabolism of ATII-cells after internalization (7). Many of C. pneumoniae-induced effects are mediated by cytokines. C. pneumoniae act at the ATII cell membrane to induce the expression of TLR4 (8). TLR signaling is partly mediated by the transcription factor NF-B, which controls the expression of many genes involved in the inflammatory response (9). C. pneumoniae-induced activation of NF-B leads to a release of the chemokine MIP-2 and the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) (8) and its receptor tumor necrosis factor receptor 1 (TNFR1). Together, they play an important role in bacterial infections and modulate the inflammatory process (10).PFC-administered as liquid (11), vapor (12), or gas (13) into the lung-represent an alternative approach to treat respiratory insufficiency. Intrat...

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Section: Discussionmentioning

confidence: 99%

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

et al. 2006

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“…Which components of Chlamydia spp and which MYD88-dependent TLRs are critical for recognition of the whole bacterium remains one of the most intriguing questions of chlamydial research (Joyee & Yang 2008). cLPS, cHSP60 and Mip have been associated as chlamydial TLR ligands (Vabulas et al 2001, Heine et al 2003, Da Costa et al 2004, Bas et al 2008. Previous studies have assigned roles for TLR2 and TLR4 receptors in recognition of Chlamydia (Darville et al 2003, den Hartog et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…PRRs like TLRs and nucleotide-binding oligomerisation domain (NOD)-like receptors play a major role in immune responses to Chlamydia infection following ligation by pathogen-associated molecular patterns (PAMPs; Vabulas et al 2001, Heine et al 2003, Prebeck et al 2003, Da Costa et al 2004, O'Connell et al 2006, Bas et al 2008, Buchholz & Stephens 2008, Joyee & Yang 2008, Chen et al 2010. It has been suggested that one of the most active PRR ligands from Chlamydia is its LPS (cLPS) and its recognition has been associated with both TLR2 and TLR4 (Heine et al 2003, Prebeck et al 2003, O'Connell et al 2006, Buchholz & Stephens 2008, Joyee & Yang 2008.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that one of the most active PRR ligands from Chlamydia is its LPS (cLPS) and its recognition has been associated with both TLR2 and TLR4 (Heine et al 2003, Prebeck et al 2003, O'Connell et al 2006, Buchholz & Stephens 2008, Joyee & Yang 2008. Chlamydia heat-shock protein 60 (cHSP60) has also been demonstrated to be able to activate immune cells in a TLR2-and TLR4-dependent fashion, although some researchers proposed that cHSP60 recognition is mainly mediated by TLR4 (Vabulas et al 2001, Da Costa et al 2004. Another Chlamydia antigen that has recently been found to strongly activate bone marrow dendritic cells is macrophage infectivity potentiator (Mip), a chlamydial lipoprotein that induces proinflammatory cytokines and chemokine production principally through TLR2 (Bas et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Chemokine response induced by Chlamydia trachomatis in prostate derived CD45+ and CD45− cells

Mackern-Oberti¹,

Breser²,

Núñez³

et al. 2011

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The role of innate cells and their receptors within the male genital tract remains poorly understood. Much less is known about the relative contribution of different genital tract cells such as epithelial/stromal cells and resident leucocytes. In this study, we examined innate immune responses to Chlamydia trachomatis by prostate epithelial/stromal cells and prostate resident leucocytes. Murine prostate primary cultures were performed and leucocyte and epithelial/stromal cells were sorted based on surface protein expression of CD45 by magnetism-activated cell sorting or fluorescence-activated cell sorting. Prostate derived CD45K and CD45C cells were infected with C. trachomatis and chemokine secretion assayed by ELISA. Similar experiments were performed using prostate CD45C and CD45K cells from myeloid differentiation factor 88 (Myd88) and Tlr4 mutant double-deficient mice. Moreover, a TLR-signalling pathway array was used to screen changes in different genes involved in TLR-signalling pathways by real-time PCR. Prostate derived CD45K and CD45C cells responded to chlamydial infection with the production of different chemokines. Both populations expressed genes involved in TLR signalling and required to respond to pathogen-associated molecular patterns and to C. trachomatis infection. Both populations required the adaptor molecule MYD88 to elicit chemokine response against C. trachomatis. TLR2-TLR4 was essential for chemokine production by CD45C prostate derived cells, but in their absence, CD45K cells still produced significant levels of chemokines. We demonstrate that C. trachomatis is differentially recognised by prostate derived CD45C and CD45K cells and suggest that diverse strategies are taking place in the local microenvironment of the host in response to the infection.

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“…However, Netea et al reported that only the TLR2-dependent pathway stimulates cytokine production by sonicated C. pneumoniae (32). In vivo studies also showed that TLR2 and TLR4 are involved in C. pneumoniae-induced cytokine release (12,40). C. pneumoniae induction of TF expression in mouse macrophages is mediated in part by early growth response factor 1 (Egr-1), signaling through TLR4, and activation of the MEK-ERK1/2 pathway.…”

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confidence: 99%

Identification and Characterization ofChlamydia pneumoniae-Specific Proteins That Activate Tumor Necrosis Factor Alpha Production in RAW 264.7 Murine Macrophages

et al. 2008

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Chlamydia pneumoniae is a common respiratory pathogen, which activates macrophages to induce inflammatory cytokines that may promote atherosclerosis. However, the antigens that induce macrophage activation have not been well defined. In the current study, three chlamydial proteins which are recognized during human infection, outer membrane protein 2 (OMP2) and two 53-kDa proteins (Cpn 0980 and Cpn 0809), were investigated to determine whether they activate macrophages and, if they do, what mechanism they use for this activation. It was shown that these three proteins could (i) induce expression of tumor necrosis factor alpha (TNF-␣) and tissue factor and (ii) induce phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) and activation of early growth response factor 1 (Egr-1). Control proteins, the N-terminal fragment of polymorphic membrane protein 8 and the thioredoxin portion of the fusion protein, had no effect on macrophages. Treatment of cells with a MEK1/2 inhibitor, U0126, dramatically reduced the phosphorylation of ERK, activation of Egr-1, and expression of TNF-␣ in macrophages treated with recombinant proteins. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the MAPK pathway. Chlamydial protein-induced expression of TNF-␣ was significantly reduced in macrophages lacking TLR2 or TLR4. These findings suggest that C. pneumoniae may activate macrophages through OMP2, Cpn 0980, and Cpn 0809 in addition to cHSP60 and that activation occurs via TLR2 or TLR4, Egr-1, and MAPK pathways.

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Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll‐like receptor 2 and 4 in vivo

Cited by 94 publications

References 30 publications

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

Chemokine response induced by Chlamydia trachomatis in prostate derived CD45+ and CD45− cells

Identification and Characterization ofChlamydia pneumoniae-Specific Proteins That Activate Tumor Necrosis Factor Alpha Production in RAW 264.7 Murine Macrophages

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