nemoci-sympt/BAKTERIALNI-INFEKCE/chlamydie/pro-infekcni-vlivy
AMK
- Chlamydia also contains several amino acid transporters including
- Aat (neutral amino acid transporter)
- XasA (amino acid antiporter)
- BrnQ-like (branched amino acid transporter)
- Number of ABC transporters (at least 13 in C. trachomatis)
- Likely associated with amino acid and oligopeptide transport [173]
- Sensitive to antimicrobial agents that inhibit microbial protein synthesis
- Such as macrolides and tetracyclines
- And that inhibit DNA replication such as quinolones. [174]
APOE4
- Epsilon4 allele at the APOE locus on (human) chromosome 19 [160]
- Enhances attachment of C.Pneumoniae elementary bodies to host cells (Gérard et al, 2008) [153]
- 3-fold more EB of strain AR-39 attach to an epsilon3 homozygous human cell line transfected with a plasmid expressing the epsilon4 coding sequence than to the same cell line harboring empty vector, vector containing an irrelevant insert sequence, or vector containing the DNA sequence encoding apoE3.
- Experiments using Chlamydophila trachomatis EB showed no enhancement of attachment in the presence of the epsilon4 allele in any assays
- Observations indicate that apoE4 enhances attachment of C. pneumoniae EB, but not those of C. trachomatis, to target host cells. [160]
ATP, GTP and UTP
- C.p. encodes enzymes that can generate
- ATP via substrate level phosphorylation
- CTP from UTP through a CTP synthetase
- Still require host cell–derived ATP, GTP and UTP [173]
- The bacteria import these nucleotides by an unusual transport system that is found only in a small number of
- Obligate intracellular bacteria
- Plant plastids
- Chlamydia species differ in their ability to metabolize nucleotides
- C. muridarum harbors guaAB-add and upp genes
- Predicted products enable ATP to GTP conversion
- Uracil phosphoribosyl tranferase-mediated biosynthesis of UTP from uracil
- C. pneumoniae
- Udk
- May mediate uridine kinase-dependent synthesis of UTP from uracil
- UMP synthetase (PyrE)
- Non-functional guaAB-add operon
- C. caviae encodes an
- Intact guaAB-add operon
- PyrE [173]
ATP8 mutation in mitochondria
- Mutation in the ATP synthase 8 (ATP8)
- Increases ROS (Yu et al., 2009)
- Leads to a mitochondrial dysfunction
- Low ATP (Schroder et al., 2016)
- Respiration rate was low [154]
- C. pneumoniae growth is promoted by a predominant mitochondrial dysfunction in fibroblasts carrying ATP8 mutation [154]
ATP5G1 knockdown of
- Knock-down of ATP synthase led to an increased infectious progeny and genome copy numbers of C.p.
- Shorter lag phase
- Also described by Juul et al. during C. pneumoniae growth under hypoxic conditions (Juul et al., 2007) [154]
Aromatic amino acid hydrolase, Cpn1046
- Uses the hosts' phenylalanine, tyrosine, and tryptophan
- Converting them to
- tyrosine, dihydroxyphenylalanine, and 5-hydroxytryptophan (Abromaitis et al, 2009) [153]
BIN1 bridging integrator 1 (Amphiphysin II )
- Required for survival of Chlamydia pneumoniae in macrophages (Gold et al, 2004) [153]
CD14 promoter polymorphism
- More frequent among patients with coronary artery disease and with C. pneumoniae DNA in peripheral blood mononuclear cells
- Than among matched C. pneumoniae-negative subjects [132]
CD14
- Binds to C.Pneumoniae on macrophages (Azenabor et al, 2005) [153]
CXCR7 chemokine (C-X-C motif) receptor 7
- Involved in entry in human coronary artery endothelial cells (Wang et al, 2010) [153]
Cholesterol
- C. pneumoniae modifies cholesterol homoeostasis in human THP-1 macrophages via JNK-PPARG dependent pathways (Liu et al, 2010 ) [153]
- Entry into epithelial cell lines is cholesterol dependent [153]
- Blocked by nystatin or filipin (Korhonen et al, 2011) [153]
DUSP1 dual specificity phosphatase 1 Knockout
- Impairs resistance to the bacterium (Rodriguez et al, 2010) [153]
EGFR epidermal growth factor receptor
- Receptor for a chlamydial invasin (pmp21)
ERK aktivace
- Infection leads to increased phosphorylation of extracellular signal-regulated map kinase (ERK)
- Activates calcium-dependent cytosolic phospholipase A2 (cPLA2)
- CPLA2 removes straight chain fatty acids from the sn2 position of host glycerophospholipids
- To generate lyso-phospholipids (Lyso-PL)
- Chlamydia-derived branched fatty acids (b-FA) are incorporated into Lyso-PL
- To generate Chlamydia-modified phospholipids (Chl-PL) [173]
FABP4 fatty acid binding protein 4
- Chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced
- Lipolysis
- Mobilization of liberated free fatty acids
- Resulting in reduced bacterial growth in adipocytes (Walenna et al, 2018) [153]
FLT3LG – fms-related tyrosine kinase 3 ligand
- Results in greater lung inflammation during acute C.Pneumoniae infection (Crother et al, 2012.) [153]
Flotillin 1
- Human flotillin-1 protein
- On Chlamydia pneumoniae growth in human line (HL) and A549 epithelial cell lines
- Colocalized with the inclusion membrane protein A (IncA) in the C. pneumoniae inclusion membranes
- Associated with IncA
- Localizes to the C. pneumoniae inclusion membrane
- Plays an important role for intracellular growth of C. pneumoniae [158]
Flotillin 1 silencing
- C. pneumoniae attachment to host cells was unaffected, but bacterial intracellular growth was attenuated in the flotillin-1-silenced cells [158]
GEM GTP binding protein
- Overexpressed in skeletal muscle
- Involved in entry in human coronary artery endothelial cells (Wang et al, 2010) [153]
Glutamate, glutamine and aspartate
- Stimulated C. pneumoniae growth more than that of C. trachomatis (Al-Younes et al, 2006) [153]
Glycolipid exoantigen (GLXA)
- Chlamydia secrete
- Binds to infected cells
- Antibodies to GXLA and complement kill the infected cells (Webley et al, 2004) [153]
Glycolysis
- Host glycolysis enhances bacterial growth in hypoxic conditions
- Abrogated chlamydial progeny by Rna silencing of:
- Phosphofructokinase (PFKP)
- Lactate dehydrogenase (LDHA)
- Glycerol-3-phosphate dehydrogenase (GPD2)
- Forkheadbox O3 (FOXO3) (Szaszák et al, 2013) [153]
- Inhibition of chlamydial glucose-6-phosphate metabolism
- Reduced C. trachomatis progeny (Engstrom et al., 2015) [154]
- Results suggest that the enhanced host cell glycolysis, caused by the hyperpolarization induced switch from OXPHOS to glycolysis,
- Promotes the increased growth of C. pneumoniae under hypoxic conditions. [154]
HLA-B – major histocompatibility complex, class I, B
- The HLA-B*35 allele is a strong-risk gene for C. pneumoniae infection (Palikhe et al, 2008) [153]
HLA-DRB1 – major histocompatibility complex, class II, DR beta 1
- HLA class II allele DRB1*0701 was positively correlated with Chlamydial hsp60 response
- DQB1*0301 and DQB1*0501 were negatively associated (Peeling et al, 1998) [153]
Heparan sulphate
- C. pneumoniae OmcB is an adhesin that binds heparan sulphate-like glycosaminoglycans (Moelleken and Hegemann, 2008) [153]
ITGB2 Integrin and complement component 3 receptor 3 and 4 subunit
- Involved in adherence to aortic epithelial cella (Kalayoglu et al, 2001) [153]
L-type calcium channel blockers
- Improving the growth of C. pneumoniae (Azenabor & Chaudhry, 2003)
Multivesicular bodies (MVB)
- Specialized subset of late endosomes
- Involved in the sorting of cargo proteins and lipids to lysosomes for degradation [173]
- Two different MVB markers, CD63 and MLN64, and the lipid LBPA (lysobisphosphatidic acid, highly enriched in intra-luminal vesicles of MVBs)
- Were found in the inclusion lumen [173]
- Inhibition of MVB biogenesis with pharmacological inhibitors or by exogenous addition of anti-CD63 antibodies
- Impairs chlamydial replication
- Disrupts the traffic of sphingomyelin and cholesterol into the inclusion [173]
- Is likely that Golgi and MVBs partially overlap in their ability to deliver essential nutrients to replicating Chlamydia [173]
- Disruption of individual components of either pathway is not sufficient to inhibit chlamydial replication [173]
- Chlamydia targets multivesicular bodies (MVB) to sequester required nutrients like sphingolipids and cholesterol. [173]
- Increases the replication of Chlamydia pneumoniae
- Prolongs its clearance in mice (Kokai et al, 2018) [153]
- Chlamydia lack biosynthetic pathways for NAD and NAD(P)
- C. pneumoniae depends on host cell derived NAD uptake
- Maintained by the ATP/ADP translocase (Fisher et al., 2013) [154]
- Chlamydia also lacks the components for NAD+ synthesis
- Essential molecule must be scavenged from the host [173]
- Nicotine stimulated chlamydial growth via cholinergic receptors in hepG2 cells, which contain these subunits (Yamaguchi et al, 2003) [153]
- Chlamydial receptor on epithelial cells (Campbell et al, 2011) [153]
- Involved in entry in human coronary artery endothelial cells (Wang et al, 2010) [153]
- Required for entry in Cho cells (Abromaitis and Stephens, 2009) [153]
- Tyrosine phosphorylation of FAK preceded its appearance in a complex with the p85 subunit of PI 3-kinase ( PIK3R1) during C.pneumoniae invasion (Coombes and Mahony, 2002) [153]
- Was found to closely mimic that of the host
- Bacteria modify host-derived glycerophospholipids
- By replacing the straight chain fatty acid at the sn2 position with a bacteria-derived branched chain fatty acid
- Sn2 deacylation of phospholipids requires phospholipase A2 (PLA2) activity
- Chlamydial genomes do not encode any obvious PLA2 homologues
- Speculated that Chlamydia relies on a host PLA2 [173]
- Pharmacological inhibition of the Ca2+-dependent cytosolic PLA2 (cPLA2)
- Prevents Chlamydia uptake of host-derived phospholipids
- Severely limits replication
- CPLA2 is activated by the extracellular signal-regulated map kinase (ERK1/2) which is fully activated during chlamydial infections
- Results suggest that Chlamydia manipulates ERK/cPLA2 signaling pathways
- To facilitate the acquisition of glycerophospholipids [173]
- CPLA2 has an innate immune signaling function in Chlamydia-infected cells
- These processes vary between host cell species [173]
- Je využívání C.p.
- Inhibition by rolipram
- Attenuated C. pneumoniae infectivity in vitro in fibroblasts (Haralambieva et al, 2004) [153]
- PDE4A PDE4B PDE4C and PDE4D are inhibited by rolipram IUPHAR [153]
- Infection of bone marrow-derived macrophages reduced in RAG1 knockouts (Rothfuchs et al, 2004) [153]
- Chlamydial species lack the enzyme necessary for SAM synthesis and scavenge it from the host via a specific transporter (Binet et al, 2011) [153]
- Chlamydial growth is attenuated in SCARB1-silenced cells (Korhonen et al, 2011) [153]
- Enhances the phagocytosis of Chlamydia into THP-1 cells (Oberley et al, 2004) [153]
- Enhances the phagocytosis of Chlamydia into THP-1 cells (Oberley et al, 2004) [153]
- Bacterial growth is iron-dependent:
- SLC40A1,
- Hepcidin (HAMP)
- Transferrin receptor (TFRC) are upregullated in the livers of infected mice (Edvinsson et al, 2017.) [153]
- Used by Chlamydia to move multiple essential compounds into the inclusion body (Fisher et al, 2012) [153]
- Protects against C.pneumoniae related inflammation
- But reduces bacterial clearance [153]
- Chlamydia acquires eukaryote-specific lipids from the host cell.
- Sphingomyelin, glucosylceramide and cholesterol
- Delivered to the inclusion
- Subsequently incorporated into chlamydial membranes [173]
- Chlamydial protein synthesis is required for sphingomyelin uptake
- Epithelial cells
- Sphingomyelin, but not glucosylceramide, is retained by the Chlamydia inclusion and EBs
- Due to preferential interception of basolaterally trafficked exocytic vesicles :[173]
- Reverses the deleterious effect of iron starvation on C.Pneumoniae survival
- Chlamydia may use iron transport pathways of the host by attracting transferrin receptors ( TFRC, TRF2 ) to the phagosome (Al-Younes et al, 1999) [153]
- Bacterial growth is iron-dependent
- SLC40A1, hepcidin (HAMP) and the transferrin receptor (TFRC)
- Are upregullated in the livers of infected mice (Edvinsson et al, 2017.) [153]
- Marginally inhibited C. trachomatis growth
- Enhance C. pneumoniae growth [153]
- Je využíván C.p.
Může to přispívat ke snížené funkci štítné žlázy ?
Může to přispívat k tomu, že po Euthyroxu mám silnější bolesti v kloubech ?
- Involved in entry in human coronary artery endothelial cells (Wang et al, 2010) [153]
- Chlamydiae import arginine from the host (Smith and Graham, 2008) [153]
- Pilot study testing the hypothesis that seropositivity to Chlamydia pneumoniae together with a specific bacteriophage protein is associated
- With first-episode myocardial infarction
- Unstable angina [138]
- C pneumoniae with phage seropositivity
- Strongly associated with the presence of abdominal aortic aneurysm [138]
- Phage association suggested
- Potential explanation for some of the variability in previous studies exploring C pneumoniae as a cause for atherosclerosis
- Only selected strains of C pneumoniae were pathogenic ? [138]
- C. pneumoniae entry into endothelial cells
- Genes encoding for components of Ca2+ trafficking system activate within minutes of the cellular contact with the bacterium
- L-type calcium channel dependent calcium ion influx C. pneumoniae–infected macrophages
- Elevated Ca2+ level mediates the ROS and NO production
- Essential for the defence against pathogenic organisms
- Results in the persistent phenotype [61]
- calcium channel blockers
- Absence of CD8+ T cells
- Cpn-infected mice have increased bacterial burdens and disease severity [120]
- Infectivity of Chlamydia can be increased with a concentration of cycloheximide
- Depresses, but not completely inhibits, the metabolism of the eucaryotic host cells
- Without affecting prokaryotic cells, like Chlamydia (Ripa & Mardh, 1977).
- Inhibits mammalian protein synthesis
- High Fe levels may not only predispose to C. pneumonia infection
- Could enhance the effects of C. pneumonia on atherogenesis [175]
- Fe modulates host defense as it in macrophages regulates their cytokine production
- Multiple mechanisms that restrict ability to obtain Fe limit microbial pathogenicity
- Hepcidin - decrease in plasma Fe concentration
- Artificial Fe starvation induced by Fe-chelating agents
- Mice Fe challenge was associated with a higher bacterial growth in peritoneal macrophages
- Fe supplementation to endothelial cells induced proliferation of C. pneumoniae
- Hepcidin-induced Fe sequestration in macrophages paradoxically enhances Fe availability for C. pneumoniae that occupy this intracellular niche
- Less efficient eradication of the bacteria and development of chronic disease !!! [175]
- Patients with high body Fe stores
- Have an increased risk of developing acute myocardial infarction
- Involve oxidative modification LDL
- C. pneumoniae growth - increased inflammation
- Decrease of body Fe store
- Proved beneficial on cardiovascular outcome if performed before the age of 60
- May also have an impact on C. pneumoniae infection
- Restriction of Fe in cell cultures of C. pneumoniae reduced bacterial growth [175]
- Regulates crucial genes involved in the adaptation to low oxygen concentrations, cell metabolism and the innate immune response
- Chlamydia pneumoniae directly interferes with host cell HIF-1alpha regulation in a biphasic manner
- C. pneumoniae infection had an additive effect on HIF-1alpha stabilization
- Resulting in enhanced glucose uptake during the early phase of infection
- Direct interference with HIF-1alpha stabilization was essential for efficient C. pneumoniae replication in hypoxia [156]
- Host cell adaptation to hypoxia was actively silenced
- By pathogen-induced HIF-1alpha degradation
- Chlamydial protease-like activity factor
- Secreted into the cytoplasm of infected cells [156]
- Promotes growth of Chlamydia pneumoniae (Szaszák et al, 2013.) [153]
- SiRNA screen of genes affecting C.Pneumoniae survival in hypoxic conditions:
- AKR1A1 AKR1B1 ALDOA AP2A1 ARRB1 C12orf5 CAMK2A CAV1 CYB5R3 CYC1 DNM2 EPAS1 FBP1 FOXO3 G6PC G6PD GLUL GPD2 HIF1A HIF3A LDHA MAPK8 MSN PFKP PGK1 PI4KA PIK3CG PXN RAB5C SIRT1 SIRT3 SLC1A5 SOD1 SOD2 STAT3 VHL VIM
- Under hypoxia, chlamydial inclusions showed increased NAD(P)H autofluorescence intensity at 48 hpi
- Quantitative analysis revealed a significantly higher NAD(P)H intensity under hypoxia compared to normoxia
- NAD(P)H from the host is acquired to overcome the lack of biosynthetic pathways for this metabolic coenzymes, indicating an increased metabolic activity of C. pneumoniae under hypoxia. [154]
- Most of the upregulated genes under hypoxia belong to the:
- Transcriptional
- Translational machinery
- Unknown function
- ATP/ADP translocase (Cpn0614) responsible for NAD uptake
- Numerous genes belonging to the energy metabolism
- Nucleotide metabolism [154]
- Indicating enhanced chlamydial metabolic activity under hypoxia [154]
- Oxygen concentration further declines due to
- Growth of intracellular pathogens
- Inflammatory processes (Kempf et al., 2005; Eltzschig and Carmeliet, 2011; Campbell et al., 2014) [154]
- Inadequate oxygen supply leads to a defective OXPHOS
- ETC activity is altered under hypoxia
- Due to the oxygen-dependent regulation of a cytochrome c oxidase (COX) subunit (Semenza, 2007)
- Low oxygen inhibits COX (Chandel et al., 1998)
- Resulting in a premature electron transfer at complex III (Semenza, 2007)
- Increasing the amount of ROS under hypoxia (Bell et al., 2007)
- Hypoxia impairs the activity of the ATP synthase
- Hyperpolarization of mitochondrial membrane potential
- Causing a switch to glycolysis (Chandel et al., 1997; Gao and Wolin, 2008)
- Induced changes in mitochondrial hyperpolarization and ROS by hypoxia
- Might play a crucial role for chlamydial growth
- Promote glycolysis
- Increase cellular longevity
- Chlamydial transporters show enhanced expression under hypoxia
- ATP/ADP translocase (Cpn0614) was upregulated under hypoxic conditions
- We suggest that the increased level of NAD(P)H in the chlamydial inclusion
- Indicated an increased need for this metabolic coenzyme leading to enhanced metabolic activity of C. pneumoniae under hypoxic conditions
- Accompanied with enhanced transcription of chlamydial genes related to glycolysis and PPP [154]
- Enhanced the replication of C. pneumoniae in embryonic fibroblasts in vitro
- IL-6 as critical for amplifying inflammation and benefiting chlamydial growth through direct effects on infected cells [8]
- Chlamydiae can actively inhibit the expression of MHC class I and class II molecules in host cells
- By secreting a chlamydial protease- or proteasome-like activity factor (CPAF) (Zhong et al., 2001)
- Is responsible for the degradation of RFX-5, a transcription factor
- Required for expression of MHC molecules
- Strategy can promote chlamydial persistence in the host cells while detection by CD4+ T cells is restrained [132]
- Inhaled glucocorticoids now have an established position in the treatment of early stages
- Negatively affect many aspects of cell-mediated immunity
- Favour the shift from a T-helper-1-type response towards a T-helper-2-type response
- May thus severely deteriorate the host's ability to eradicate an intracellular pathogen, such as Chlamydia pneumoniae
- Able to reactivate persistent Chlamydia to an active growth phase !!! [22]
- Increasing the production of pro-inflammatory cytokines at the site of infection
- Can further amplify inflammation in the airways of patients with asthma !!! [22]
- Use of high-dose inhaled steroids (x low-dose) was associated with:
- Increase in specific IgG and IgA titres [22]
- Lower forced expiratory volume in 1 second percentage of the predicted value [22]
- Elevated IgA titres were associated with a higher daytime symptom score
- May thus be associated with markers of asthma severity [22]
- Glucocorticoids reduce pulmonary eosinophilia and cytokine production in the lungs
- By effector T-cells
- Most potent anti-inflammatory drugs available for the treatment of asthma
- Average doses of inhaled corticosteroids have gradually increased during the past decade
- Important, although often neglected impact of glucocorticoids on Th1/Th2 balance
- Glucocorticoids shift the Th1/Th2 cytokine balance towards a Th2-type response
- Most important determinants in the micro-environment
- Complexity
- Difficulties in examining the interactions in vitro
- May have a genetic basis
- Combination with secondary factors
- Downregulation of cell-mediated immunity (Th1)
- Upregulation of humoral immunity (Th2)
- C. pneumoniae, as an intracellular parasite
- Requires a strong and intact cell-mediated immune response to be eradicated [22] !!!
- Inhibits the release of pro-inflammatory cytokines from human lung epithelial cells and alveolar macrophages cells
- One of the central effects of glucocorticoids, justifying their use in asthma therapy
- Leading to poor stimulation of antigen presentation and T-cells
- Poor activation of phagocytes
- Impaired ability of the host to elicit innate immunity [22]
- Inhibition of IL-12 production in macrophages/monocytes and dendritic cells
- Major mechanism by which glucocorticoids affect cytokine synthesis
- IL-12 is the key cytokine in regulating innate and adoptive immunity
- It induces IFN-gamma production
- Enhances cytolytic activity of CD4+ and CD8+ T-cells and natural killer (NK) cells [22]
- IL-12 is fundamental to the development of cell-mediated immunity (Th1) protective against intracellular organisms
- Absence of IL-12 early in the infection results in
- Impaired activation of innate immunity
- Development of a Th2-type response with IL-4 production
- Detrimental to the control of an intracellular infection [22]
- Reduced production of IL-12 in corticosteroid-treated human macrophages result in
- Decreased ability of T-cells to induce IFN-gamma
- Increased ability to induce IL-4 production [22]
- Stimulate the production of TGF-ß and IL-10 by monocytes
- IL-10 is an anti-inflammatory
- Inhibits IFN-gamma production from T-cells
- By suppressing IL-12 production from macrophages and dendritic cells
- IL-10 inhibits cytokine production from Th1, NK, monocyte/macrophage and dendritic cells
- Suppresses cell-mediated immunity [22]
- Glucocorticoid-induced increase in IL-10 production ameliorates the inflammation
- Severely deteriorates the host's ability to resolve an intracellular infection [22]
- Reduces the IFN-gamma production in NK and Th cells
- Further favouring the establishment of a persistent chlamydial infection [22]
- Glucocorticoid induced increase in TGF-beta level in asthmatics
- TGF-beta is an anti-inflammatory/suppressory cytokine
- Antiproliferative activity on macrophages, endothelial cells, and T- and B-cells
- Inhibits the induction of NK cell activities
- Reduces cellular expression of class II major histocompatibility complex (MHC) protein [22]
- TGF-ß and IFN-?
- Reciprocally regulated [22]
- Decrease in NK cell activity
- Direct effect on those cells
- Depletion of active NK cells result in a shift from a Th1 dominant response to a more of a Th2 response
- Severely impaired early IFN-? production in the absence of properly functioning NK cells
- Early NK cell response may be an important feature of intracellelar infections [22]
- Corticosteroids can enhance the production of reactive oxygen species by the monocytes that are excited by Chlamydia toxins [67]
- Beneficial anti- inflammatory and anti-atherosclerosis effects of these steroids are cancelled [67]
- The main anti-inflammatory effects of corticosteroids are:
- Inhibition of cytokine production
- Steroids block so the exponential amplification of monocyte auto- stimulation
- Suppression of the adhesion molecules produced by the excited cells and responsible for the adhesion to the vascular wall [67]
- A prolonged corticotherapy would even result in a higher atherosclerosis incidence (Kalbak, 1972, Ann Rheum Dis. 31: 196-200; Troxler et al . , 1977, Atherosclerosis 26: 151- 162) [67]
- Elevated corticosteroid doses, a prolonged corticotherapy can
- Induce accumulation of abdominal fat
- Insulin-resistance
- Arterial hypertension
- Hyperlipidemia (Nashel, 1986, Am J Med 80: 925-929; Despres et al . , 1990, Arteriosclerosis 10: 497- 511) [67]
- Corticosteroids affect the natural resistance of humans to Chlamyida infections and/or to increase C. pneumoniae growth in vi tro
- Grayston, 1998, Circulation 97: 1669-1770;
- Malinverni et al . , 1995, J. Infect. Dis . 172: 593-594;
- Laitinen et al . , 1996, Infect. Immun. 64: 1488- 1490;
- Tsumura et al . , 1996, J. Clin. Microbiol . 34: 2379- 2381 [67]
- Corticosteroids increase C. pneumoniae infection (Malinverni et al., 1995)
- The combination of SS (scond hand smoke) exposure and Cpn infection enhanced atherosclerosis more than either variable did independently
- By activating inflammatory cells
- By promoting growth and maturation of lesions
- Via defective phagocytic clearance
- Accumulation of apoptotic cells [165]
- Endoplasmic reticulum-derived organelles
- Composed of a
- Neutral lipid core
- Surrounded by a phospholipid monolayer [173]
- Lipid storage compartments
- Dynamic organelles
- Involved in a multiple biological processes
- Proliferate + recruited to the periphery of the inclusion during Chlamydia infection [173]
- Chlamydial proteins (Lda1 , 2 and 3)
- Potentially involved in targeting LDs
- Ability to localize to LDs in mammalian cells [173]
- LDs enter into the inclusion lumen [173]
- Intact organelles can be translocated into the inclusion
- Vesicle fusion is not the only means to deliver potential nutrients
- Pharmacological inhibition of neutral lipid biosynthesis, and thus LD biogenesis
- Impairs chlamydial development [173]
- Lipid droplets, the main store of neutral lipids, are targeted by Chlamydia lipid droplet-associated proteins (Lda) and translocated into the inclusion
- C. pneumoniae can infect phagocytic cells, especially macrophages
- Use them as host cells (Godzik et al., 1995; Mannonen et al., 2004)
- Can enhance replication and dissemination of the infection from the respiratory tract to other locations (Moazed et al., 1998) [132]
- Can suppress the immune system
- Increase your risk of developing pneumonia
- More often of C. pneumoniae seroconversion (Rantala et al., 2008) [132]
- C. trachomatis
- Inhibition of infection in HeLa 229 cells [132]-MBL variant alleles
- Associated with accelerated development of severe atherosclerosis (Madsen et al., 1998)
- C. pneumoniae infection may promote development of severe coronary artery disease in predisposed individuals (Rugonfalvi-Kiss et al., 2002)
- MBL polymorphism could be associated with tubal damage following C. trachomatis infection (Sziller et al., 2007) [132]
- Chlamydia needs pyrimidine and purine nucleotides for
- Energy transduction
- Nucleic acid biosynthesis [173]
- Unable to synthesize them de novo [173]
- Essential amino acid for chlamydiae
- Reduction of its availability might disturb intracellular growth of the pathogen [35]
- Intracellular growth of C. pneumoniae is regulated by the modulation of activity of indoleamine 2,3-dioxygenase
- Cleaves l-tryptophan [56]
- IFN-? produced by T lymphocytes and natural killer cells regulates the synthesis of IDO, catabolizing tryptophan to its two metabolites
- Results in a depletion of tryptophan pools within the host cell
- When tryptophan levels are depleted, C. pneumoniae growth is arrested.
- Upon the addition of excess tryptophan
- Replication was restored [19]
- Mast cells
- Insufficient supply of nutrients such as iron [99]
- An endothelial response to chronic infection of CMV and C. pneumoniae may be enhanced by intracellular iron [99]
- Pokles TH1, převaha TH2
- Significantly more likely to be C. pneumoniae-IgG-seropositive (IgG?1:16) [14]
- Current smoking was associated with a higher prevalence of circulating C. pneumoniae DNA detection [14]
- More susceptible to C. pneumoniae infection than women [14]
- Vyšší hladiny železa [14]
- In general higher in men than in women
- Known to be essential for developing microbial infection
- Growth of C. pneumoniae in a human Hep-2 cells strongly inhibited
- By iron restriction
- By the use of an iron-chelating compound [14]
- Iron up-regulates C. pneumoniae-induced
- VCAM-1 (vascular cell adhesion molecule-1) expression
- ICAM-1 (intercellular adhesion molecule-1) expression on ECs [14]
- Enhance the effects of C. pneumoniae on atherogenesis [14]
- [22]
- Impaired immune responses in ApoE-deficient mice [100]
- Lipoprotein metabolism [100]
N-acetyl cysteine
NAD
CHRNA4 CHRNA7 CHRNB2 CHRNB4 Nicotinic acteylcholine receptors
OLR1 oxidized low density lipoprotein (lectin-like) receptor 1
PDGFB platelet-derived growth factor beta polypeptide
PDIA2 – protein disulfide isomerase family A, member 2
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha)
Lipid composition of chlamydial membranes and PLA2
Phenylalanine
Phosphodiesterase 4
RAG1 – recombination activating gene 1
S-adenosylmethionine (SAM)
SCARB1 scavenger receptor class B, member 1
SFTPA1 – surfactant protein A1
SFTPD – surfactant protein D
SLC40A1 solute carrier family 40 member 1 (ferreportin)
SLC5A6 solute carrier family 5 (sodium-dependent vitamin transporter), member 6
SOCS1 suppressor of cytokine signaling 1
Sphingomyelin, glucosylceramide and cholesterol
TF transferrin
TFRC Transferrin receptor
Tryptophan and valine
Tyrosine
VEGFA vascular endothelial growth factor A
Arginin
Asthma
<2>Bacteriophage of Chlamydia pneumonia
Blokátory vápníkových kanálů (verapamil, isradipin aj.)
CD8+ T cells depletion
Chemotherapy
Chronic obstructive pulmonary diseases (COPD)
Cycloheximide
Diabetes
Fe
Heart disease
Hypoxia-inducible factor-1 (HIF-1)
In hypoxia
Late phase of intracellular chlamydial replication
Hypoxie - Host metabolism in a low oxygen environment
IL-6
Inhibice exprese of MHC class I and class II
Kortikoidy a C.pneunmonia in Non-atopic asthma
Přesně tak to bylo. Vždy po cca týdnu až 14 dnech foukání kortikoidů se mi objevil kašel a zhoršení dušnosti a pocitu nemocnosti, a proto jsem tuto léčbu i přes všechny lékařské řeči odmítnula. Prostě to nebylo ono. Mnohaleté potátěžové astma s enormní bolestivostí po nadýchání se suchého nebo studeného vzduchu zmizelo až po oapkovaném přeléčení se antibiotiky.
Kouření
Leukemia
Lipid droplets (LD)
Makrofágy v plicní tkáni
Koinfekce jinou resp. chorobou
Chronický zánět
Zvýšená plicní prppustnost
Kouření aj. cizorodé partikule v plicích
Alfa 1 antitrypsinová deficience
Mnoho jiných vlivů
Malnutrition
Mannose-binding lectin (MBL) 2 gene polymorphism
Nukleotidy
Může tedy být dna rizikovým faktorem pro zrychlený růst C. pneumonia ?
Parkinson's disease
Převaha Th2 imunity
Radiation
Stroke
Tryptophan
Další rizikové faktory
Asthma
Alfa-1-antitrypsinová deficience
Zvýšená plicní propustnost
Hypercholesterolemie
Inhibice TNF alfa
Pokles IFN-gamma
Nedostatek Fe
Pokles buněčné imunity
Smokers
Men
Higher iron levels
Advanced age
Concomitant diseases
Glucocorticoid usage
Hereditary factors
knock-out ApoE
