Chlamydia pneumoniae: crossing the barriers?

[Guest guest]

Fabulous article summarizing and detailing ways in

which Cpn actively uses monocytes and macrophages to

move from respiratory into other tissues. I was

especially interested to note " ... induce a

functionally active, adhesive state in monocytic cells

by activation of the integrin adhesion receptor

system. Therefore, C. pneumoniae is not just

transported into the subendothelium by monocytes as an

innocent bystander, but can actively contribute to the

monocyte recruitment to the preferential sites of

atherosclerotic lesions. Moreover, this study suggests

that C. pneumoniae-infected circulating monocytes may

have the capacity to induce an adhesive phenotype in

adjacent, noninfected monocytes... "

Anyone know of ways to interfere with " integrin

adhesion receptor system? "

Jim

http://erj.ersjournals.com/cgi/content/full/23/4/499

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PubMed Citation

Articles by Blasi, F.

Articles by Allegra, L.

Eur Respir J 2004; 23:499-500

Copyright ©ERS Journals Ltd 2004

Chlamydia pneumoniae: crossing the barriers?

F. Blasi1, S. Centanni2 and L. Allegra1

1 Institute of Respiratory Diseases, University of

Milan, IRCCS Ospedale Maggiore di Milano, and 2

Institute of Respiratory Diseases, University of

Milan, Respiratory Unit, San Paolo Hospital, Milan,

Italy

Correspondence: F. Blasi, Institute of Respiratory

Diseases, University of Milan, Pad. Litta, IRCCS

Ospedale Maggiore di Milano, via F. Sforza, 35,

I-20122 Milano, Italy. Fax: 39 0250320628. E-mail:

francesco.blasi@...

Chlamydia pneumoniae has been recognised as a cause of

respiratory tract infections and implicated as a

potential risk factor or causative agent in different

extrapulmonary diseases including atherosclerosis,

multiple sclerosis, and Alzheimer's disease 1–3. Being

an obligate intracellular bacterium, C. pneumoniae has

been detected in circulating monocytes and can

activate inflammatory processes in epithelial,

endothelial and smooth muscle cells in vitro 4.

In the present issue of the European Respiratory

Journal (ERJ), Gieffers et al. 5 report an animal

model showing that intratracheal infection with C.

pneumoniae is followed by systemic dissemination of

the infection mediated by peripheral blood mononuclear

cells (PBMCs). The authors, on the basis of both the

animal model and in vitro study results, hypothesise a

" cellular model " for C. pneumoniae dissemination.

Infection of the lung is characterised by an early

phase dominated by granulocytes, and a late phase

dominated by alveolar macrophages. Alveolar

macrophages, infected by granulocytes, would migrate

through the mucosal barrier, using lymphatic tissue,

and gain access to the systemic circulation as PBMCs

reaching the spleen and the vasculature. The

conclusions are mostly inferred on the basis of cell

morphology in the absence of definitive determination

of infected cell types in extra-pulmonary tissues.

Nonetheless, the proposed " cellular model " hypothesis

is intriguing and undoubtedly consistent with other

recently published studies.

Wark et al. 6 analysed the relationship between airway

inflammation and serological response to C. pneumoniae

in acute severe asthma. At presentation with acute

asthma, the sputum total cell count was increased in

C. pneumoniae antibody responders compared to

nonresponders, and C. pneumoniae responders had

significantly more sputum neutrophils compared to

nonresponders. Moazed et al. 7 demonstrated that

monocytes may act as vectors and systemically

disseminate C. pneumoniae, and Blasi et al. 8 showed a

good correlation between C. pneumoniae detection in

PBMCs and in atherosclerotic plaques. However, in

order to adhere and migrate through the vessel wall,

monocytes have to go through a highly coordinated

process, which requires the activation of different

adhesion receptors in a cascade-like fashion. May et

al. 9 report that C. pneumoniae infection induces

rolling and adhesion of macrophages to the noninflamed

vessel wall of noninfected, nonatherosclerotic mice.

C. pneumoniae-infected monocytic cells show enhanced

transmigration and attach to the endothelium via the

activated integrins very late antigen 4 (VLA-4), and

the activation of the two ß2-integrins lymphocyte

function-associated antigen-1 (LFA-1) and macrophage

antigen-1 (MAC-1), involving the urokinase receptor

(uPAR). This study demonstrates that C.

pneumoniae-infected monocytes may be armed to invade

noninflamed subendothelium and initiate inflammatory

processes. The data indicate that C. pneumoniae has

the potential to induce a functionally active,

adhesive state in monocytic cells by activation of the

integrin adhesion receptor system. Therefore, C.

pneumoniae is not just transported into the

subendothelium by monocytes as an innocent bystander,

but can actively contribute to the monocyte

recruitment to the preferential sites of

atherosclerotic lesions. Moreover, this study suggests

that C. pneumoniae-infected circulating monocytes may

have the capacity to induce an adhesive phenotype in

adjacent, noninfected monocytes.

Monocytes perhaps also act as the vehicle for

trafficking C. pneumoniae across the blood/brain

barrier. PBMCs may function as a means by which C.

pneumoniae enters the central nervous system (CNS) to

induce neuroinflammation in Alzheimer's disease and in

multiple sclerosis 10. C. pneumoniae infection has

been shown to stimulate transendothelial entry of

monocytes through human brain endothelial cells

(HBMEC). This entry is facilitated by the upregulation

of vascular cell adhesion molecule-1 and intercellular

adhesion molecule-1 on HBMECs and a corresponding

increase of LFA-1, VLA-4, and MAC-1 on monocytes.

An association between C. pneumoniae and multiple

sclerosis has been proposed, based on the higher

frequency of its detection in the cerebrospinal fluid

(CSF) of multiple sclerosis patients compared to

neurological controls. Multiple sclerosis is an

inflammatory demyelinating disease of the CNS of

unknown etiology. Current knowledge supports a

multifactorial aetiology in which both genetic and

environmental factors (including microbial agents) may

concur. Interestingly, experimental autoimmune

encephalomyelitis (EAE), the experimental animal model

of multiple sclerosis, has been successfully induced

using a C. pneumoniae peptide analogue of rat myelin

basic protein 11. Although multiple sclerosis and EAE

are obviously two different entities, this study

provides the first indication of a possible direct

contribution of C. pneumoniae to the pathophysiology

of (experimental) demyelination. The presence of C.

pneumoniae in human CSF does not actually prove that

the organism causes or triggers multiple sclerosis:

chlamydial infection of the CNS may just represent an

opportunistic, secondary event in the disease. Even in

this case, however, the presence of the organism may

exacerbate/modulate a pre-existing pathogenic process.

This is also supported by the finding that C.

pneumoniae polymerase chain reaction (PCR)-positive

patients have more active lesions than C. pneumoniae

PCR-negative/patients suggesting a role for C.

pneumoniae in fostering chronic inflammatory

stimulation within the CNS 2. It can be hypothesised

that C. pneumoniae might act as cofactor capable of

fuelling previously established inflammatory and

demyelinating processes and promote a more active

disease.

Gieffers et al. 5 showed a good correlation between

the presence of C. pneumoniae in PBMCs both in the

lung and in the vasculature. These data are consistent

with the results reported by Blasi and co-workers 8,

12 who showed that C. pneumoniae DNA identification is

similar in biopsy specimens (vascular and bronchial)

and PBMCs, which suggests that blood PCR may be a

useful tool for identifying patients with chronic C.

pneumoniae infection.

Clinical persistence is probably a key concept in C.

pneumoniae infection pathogenesis. Microbial

persistence is a state of infection during which the

host immune response does not eliminate the pathogen,

thereby resulting in continuing damage to the host.

Persistent infection may amplify airway inflammation

in asthma and chronic obstructive pulmonary disease

(COPD), but also in extrapulmonary diseases such as

atherosclerosis, multiple sclerosis and Alzheimer's

disease.

s 13 has recently revised the possible

pathogenic mechanisms of C. pneumoniae infection. He

underlines that C. pneumoniae can induce an

inflammatory process elicited by infected host cells

that is necessary and sufficient to account for

chronic and intense inflammation and the promotion of

cellular proliferation, tissue remodelling and

scarring, the ultimate causes of disease sequelae.

The cellular responses of epithelial cells, the

primary home for C. pneumoniae, can be reliably

induced upon acute, chronic and persistent infection.

The cellular processes of the epithelial cells,

elicited by chlamydial infection, cause the influx of

inflammatory neutrophils, T-cells, B-cells and

macrophages that are stimulated by the

pro-inflammatory cytokine and chemokine environment.

These cells become activated in both

antigen-nonspecific and, for re-infection,

antigen-specific responses to produce their own

repertoire of cytokines and growth factors. The

induction of host cell cytokines will promote foci of

inflammatory responses in addition to promoting

cellular proliferation, tissue remodelling and healing

processes that, if persistent, result in scarring.

The possible role of chronic-persistent infection is

suggested in asthmatic children where persistent

clinical features are associated with C. pneumoniae

infection, indicating that this infection should be

investigated and treated in case of persistent

asthmatic symptoms 14–15. On the other hand, in adults

with asthma, higher titres of antibodies directed

against C. pneumoniae are associated with more severe

clinical disease 16. The intense neutrophil influx

demonstrated in acute severe asthma is potentially a

potent source of proteolytic enzymes with the ability

to damage and activate the airway epithelium, whereas

neutrophil elastase can cause eosinophil degranulation

6. The inflammatory changes caused by infection with

C. pneumoniae have the potential to amplify the

inflammation and airway damage present in asthma.

Furthermore, standard asthma treatment may potentially

enhance this response, given the ability of

corticosteroids to reactivate C. pneumoniae infection.

These data suggest that C. pneumoniae infection may

influence the clinical course of asthma.

In the same way, preliminary data on chronic infection

with C. pneumoniae in patients with COPD and its

interaction with host cells indicate that this agent

may be implicated in the modulation of the natural

history of chronic bronchitis and emphysema 12.

The interesting finding of the study by Gieffers et

al. 5 is the demonstration that granulocytes are one

of the main target of C. pneumoniae infection and that

these cells can act as " infecting " cells and reservoir

of the pathogen. These data confirm the excellent

capacity of C. pneumoniae to survive in different

immune cells, use the immune cells as carriers for

breaching the blood-tissue barriers, and potentially

cause chronic/persistent infections.

Chronic infection is probably the real challenge in

Chlamydia pneumoniae infection and we certainly need

new studies addressing the question whether Chlamydia

pneumoniae long-term survival within immune and

nonimmune cells has a role in chronic pulmonary and

extrapulmonary diseases.

References

Neuman FJ. Chlamydia pneumoniae-atherosclerosis link:

a sound concept in search for clinical relevance.

Circulation 2002;106:2414–2416.[Free Full Text]

Grimaldi LM, Pincherle A, elli-Boneschi F, et

al. An MRI study of Chlamydia pneumoniae infection in

Italian multiple sclerosis patients. Mult Scler

2003;9:467–471.[CrossRef][iSI][Medline] [Order article

via Infotrieve]

Blain BJ, Gerard HC, Arking EJ, et al. Identification

and localization of Chlamydia pneumoniae in the

Alzheimer's brain. Med Microbiol Immunol

1998;187:23–42.[CrossRef][iSI][Medline] [Order article

via Infotrieve]

Dechend R, Maass M, Gieffer J, et al. Chlamydia

pneumoniae infection of vascular smooth muscle and

endothelial cells activates NF-B and induces tissue

factor and PAI-1 expression: a potential link to

accelerated arteriosclerosis. Circulation

1999;100:1369–1373.[Abstract/Free Full Text]

Gieffers J, van Zandbergen G, Rupp J, et al.

Phagocytes transmit Chlamydia pneumoniae from the lung

to the vasculature. Eur Respir J

2004;23:506–510.[Abstract/Free Full Text]

Wark PAB, ston SL, Simpson JL, Hensley MJ, Gibson

PG. Chlamydia pneumoniae immunoglobulin A reactivation

and airway inflammation in acute asthma. Eur Respir J

2002;20:834–840.[Abstract/Free Full Text]

Moazed TC, Kuo CC, Grayston JT, LA. Evidence

of systemic dissemination of Chlamydia pneumoniae via

macrophages in the mouse. J Infect Dis

1998;177:1322–1325.[iSI][Medline] [Order article via

Infotrieve]

Blasi F, Boman J, Esposito G, et al. Chlamydia

pneumoniae DNA detection in peripheral blood

mononuclear cells is predictive of vascular infection.

J Infect Dis

1999;180:2074–2076.[CrossRef][iSI][Medline] [Order

article via Infotrieve]

May AE, Redecke V, Grüner S, et al. Recruitment of

Chlamydia pneumoniae-infected macrophages to the

carotid artery wall in noninfected, nonatherosclerotic

mice. Arterioscler Thromb Vasc Biol

2003;23:789–794.[Abstract/Free Full Text]

MacIntyre A, Abramov R, Hammond CJ, et al. Chlamydia

pneumoniae infection promotes the transmigration of

monocytes through human brain endothelial cells. J

Neurosci Res 2003;71:740–750.[CrossRef][iSI][Medline]

[Order article via Infotrieve]

Lenz DC, Lu L, Conant SB, et al. A Chlamydia

pneumoniae-specific peptide induces experimental

autoimmune encephalomyelitis in rats. J Immunol

2001;167:1803–1808.[Abstract/Free Full Text]

Blasi F, Damato S, Cosentini R, et al. Chlamydia

pneumoniae and chronic bronchitis: association with

severity and bacterial clearance following treatment.

Thorax 2002;57:672–676.[Abstract/Free Full Text]

s RS. The cellular paradigm of chlamydial

pathogenesis. TRENDS Microbiol

2003;11:44–51.[CrossRef][iSI][Medline] [Order article

via Infotrieve]

Cunningham AF, ston SL, Julious SA, Lampe FC, Ward

ME. Chronic Chlamydia pneumoniae infection and asthma

exacerbations in children. Eur Respir J

1998;11:345–349.[Abstract/Free Full Text]

Thumerelle C, Deschildre A, Bouquillon C, et al. Role

of viruses and atypical bacteria in exacerbations of

asthma in hospitalized children: a prospective study

in the Nord-Pas de Calais region (France). Pediatr

Pulmonol 2003;35:75–82.[CrossRef][iSI][Medline] [Order

article via Infotrieve]

ten Brinke A, van Dissel JT, Sterk JT, Zwinderman AH,

Rabe KF, Bel EH. Persistent airflow limitation in

adult-onset nonatopic asthma is associated with

serologic evidence of Chlamydia pneumoniae infections.

J Allergy Clin Immunol

2001;107:449–454.[CrossRef][iSI][Medline] [Order

article via Infotrieve]

[Guest guest]

Maybe the ing/Rath Protocol plays into this very senario and

vitamin C supplemented with proline and lysine are beneficial at

some point in this mechanism?

- In infections , Jim Kepner

<jimk192002@y...> wrote:

> Fabulous article summarizing and detailing ways in

> which Cpn actively uses monocytes and macrophages to

> move from respiratory into other tissues. I was

> especially interested to note " ... induce a

> functionally active, adhesive state in monocytic cells

> by activation of the integrin adhesion receptor

> system. Therefore, C. pneumoniae is not just

> transported into the subendothelium by monocytes as an

> innocent bystander, but can actively contribute to the

> monocyte recruitment to the preferential sites of

> atherosclerotic lesions. Moreover, this study suggests

> that C. pneumoniae-infected circulating monocytes may

> have the capacity to induce an adhesive phenotype in

> adjacent, noninfected monocytes... "

>

> Anyone know of ways to interfere with " integrin

> adhesion receptor system? "

> Jim

>

> http://erj.ersjournals.com/cgi/content/full/23/4/499

>

> HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE

> OF CONTENTS

>

> QUICK SEARCH: [advanced]

>

> Author:

> Keyword(s):

>

> Year: Vol: Page:

>

>

> This Article

>

> Full Text (PDF)

> Alert me when this article is cited

> Alert me if a correction is posted

> Citation Map

>

> Services

>

> Email this article to a friend

> Similar articles in this journal

> Similar articles in ISI Web of Science

> Similar articles in PubMed

> Alert me to new issues of the journal

> Download to citation manager

> Search for citing articles in:

> ISI Web of Science (1)

>

> PubMed

>

> PubMed Citation

> Articles by Blasi, F.

> Articles by Allegra, L.

> Eur Respir J 2004; 23:499-500

> Copyright ©ERS Journals Ltd 2004

> Chlamydia pneumoniae: crossing the barriers?

>

> F. Blasi1, S. Centanni2 and L. Allegra1

> 1 Institute of Respiratory Diseases, University of

> Milan, IRCCS Ospedale Maggiore di Milano, and 2

> Institute of Respiratory Diseases, University of

> Milan, Respiratory Unit, San Paolo Hospital, Milan,

> Italy

>

> Correspondence: F. Blasi, Institute of Respiratory

> Diseases, University of Milan, Pad. Litta, IRCCS

> Ospedale Maggiore di Milano, via F. Sforza, 35,

> I-20122 Milano, Italy. Fax: 39 0250320628. E-mail:

> francesco.blasi@u...

>

> Chlamydia pneumoniae has been recognised as a cause of

> respiratory tract infections and implicated as a

> potential risk factor or causative agent in different

> extrapulmonary diseases including atherosclerosis,

> multiple sclerosis, and Alzheimer's disease 1–3. Being

> an obligate intracellular bacterium, C. pneumoniae has

> been detected in circulating monocytes and can

> activate inflammatory processes in epithelial,

> endothelial and smooth muscle cells in vitro 4.

>

> In the present issue of the European Respiratory

> Journal (ERJ), Gieffers et al. 5 report an animal

> model showing that intratracheal infection with C.

> pneumoniae is followed by systemic dissemination of

> the infection mediated by peripheral blood mononuclear

> cells (PBMCs). The authors, on the basis of both the

> animal model and in vitro study results, hypothesise a

> " cellular model " for C. pneumoniae dissemination.

> Infection of the lung is characterised by an early

> phase dominated by granulocytes, and a late phase

> dominated by alveolar macrophages. Alveolar

> macrophages, infected by granulocytes, would migrate

> through the mucosal barrier, using lymphatic tissue,

> and gain access to the systemic circulation as PBMCs

> reaching the spleen and the vasculature. The

> conclusions are mostly inferred on the basis of cell

> morphology in the absence of definitive determination

> of infected cell types in extra-pulmonary tissues.

> Nonetheless, the proposed " cellular model " hypothesis

> is intriguing and undoubtedly consistent with other

> recently published studies.

>

> Wark et al. 6 analysed the relationship between airway

> inflammation and serological response to C. pneumoniae

> in acute severe asthma. At presentation with acute

> asthma, the sputum total cell count was increased in

> C. pneumoniae antibody responders compared to

> nonresponders, and C. pneumoniae responders had

> significantly more sputum neutrophils compared to

> nonresponders. Moazed et al. 7 demonstrated that

> monocytes may act as vectors and systemically

> disseminate C. pneumoniae, and Blasi et al. 8 showed a

> good correlation between C. pneumoniae detection in

> PBMCs and in atherosclerotic plaques. However, in

> order to adhere and migrate through the vessel wall,

> monocytes have to go through a highly coordinated

> process, which requires the activation of different

> adhesion receptors in a cascade-like fashion. May et

> al. 9 report that C. pneumoniae infection induces

> rolling and adhesion of macrophages to the noninflamed

> vessel wall of noninfected, nonatherosclerotic mice.

> C. pneumoniae-infected monocytic cells show enhanced

> transmigration and attach to the endothelium via the

> activated integrins very late antigen 4 (VLA-4), and

> the activation of the two ß2-integrins lymphocyte

> function-associated antigen-1 (LFA-1) and macrophage

> antigen-1 (MAC-1), involving the urokinase receptor

> (uPAR). This study demonstrates that C.

> pneumoniae-infected monocytes may be armed to invade

> noninflamed subendothelium and initiate inflammatory

> processes. The data indicate that C. pneumoniae has

> the potential to induce a functionally active,

> adhesive state in monocytic cells by activation of the

> integrin adhesion receptor system. Therefore, C.

> pneumoniae is not just transported into the

> subendothelium by monocytes as an innocent bystander,

> but can actively contribute to the monocyte

> recruitment to the preferential sites of

> atherosclerotic lesions. Moreover, this study suggests

> that C. pneumoniae-infected circulating monocytes may

> have the capacity to induce an adhesive phenotype in

> adjacent, noninfected monocytes.

>

> Monocytes perhaps also act as the vehicle for

> trafficking C. pneumoniae across the blood/brain

> barrier. PBMCs may function as a means by which C.

> pneumoniae enters the central nervous system (CNS) to

> induce neuroinflammation in Alzheimer's disease and in

> multiple sclerosis 10. C. pneumoniae infection has

> been shown to stimulate transendothelial entry of

> monocytes through human brain endothelial cells

> (HBMEC). This entry is facilitated by the upregulation

> of vascular cell adhesion molecule-1 and intercellular

> adhesion molecule-1 on HBMECs and a corresponding

> increase of LFA-1, VLA-4, and MAC-1 on monocytes.

>

> An association between C. pneumoniae and multiple

> sclerosis has been proposed, based on the higher

> frequency of its detection in the cerebrospinal fluid

> (CSF) of multiple sclerosis patients compared to

> neurological controls. Multiple sclerosis is an

> inflammatory demyelinating disease of the CNS of

> unknown etiology. Current knowledge supports a

> multifactorial aetiology in which both genetic and

> environmental factors (including microbial agents) may

> concur. Interestingly, experimental autoimmune

> encephalomyelitis (EAE), the experimental animal model

> of multiple sclerosis, has been successfully induced

> using a C. pneumoniae peptide analogue of rat myelin

> basic protein 11. Although multiple sclerosis and EAE

> are obviously two different entities, this study

> provides the first indication of a possible direct

> contribution of C. pneumoniae to the pathophysiology

> of (experimental) demyelination. The presence of C.

> pneumoniae in human CSF does not actually prove that

> the organism causes or triggers multiple sclerosis:

> chlamydial infection of the CNS may just represent an

> opportunistic, secondary event in the disease. Even in

> this case, however, the presence of the organism may

> exacerbate/modulate a pre-existing pathogenic process.

> This is also supported by the finding that C.

> pneumoniae polymerase chain reaction (PCR)-positive

> patients have more active lesions than C. pneumoniae

> PCR-negative/patients suggesting a role for C.

> pneumoniae in fostering chronic inflammatory

> stimulation within the CNS 2. It can be hypothesised

> that C. pneumoniae might act as cofactor capable of

> fuelling previously established inflammatory and

> demyelinating processes and promote a more active

> disease.

>

> Gieffers et al. 5 showed a good correlation between

> the presence of C. pneumoniae in PBMCs both in the

> lung and in the vasculature. These data are consistent

> with the results reported by Blasi and co-workers 8,

> 12 who showed that C. pneumoniae DNA identification is

> similar in biopsy specimens (vascular and bronchial)

> and PBMCs, which suggests that blood PCR may be a

> useful tool for identifying patients with chronic C.

> pneumoniae infection.

>

> Clinical persistence is probably a key concept in C.

> pneumoniae infection pathogenesis. Microbial

> persistence is a state of infection during which the

> host immune response does not eliminate the pathogen,

> thereby resulting in continuing damage to the host.

> Persistent infection may amplify airway inflammation

> in asthma and chronic obstructive pulmonary disease

> (COPD), but also in extrapulmonary diseases such as

> atherosclerosis, multiple sclerosis and Alzheimer's

> disease.

>

> s 13 has recently revised the possible

> pathogenic mechanisms of C. pneumoniae infection. He

> underlines that C. pneumoniae can induce an

> inflammatory process elicited by infected host cells

> that is necessary and sufficient to account for

> chronic and intense inflammation and the promotion of

> cellular proliferation, tissue remodelling and

> scarring, the ultimate causes of disease sequelae.

>

> The cellular responses of epithelial cells, the

> primary home for C. pneumoniae, can be reliably

> induced upon acute, chronic and persistent infection.

> The cellular processes of the epithelial cells,

> elicited by chlamydial infection, cause the influx of

> inflammatory neutrophils, T-cells, B-cells and

> macrophages that are stimulated by the

> pro-inflammatory cytokine and chemokine environment.

> These cells become activated in both

> antigen-nonspecific and, for re-infection,

> antigen-specific responses to produce their own

> repertoire of cytokines and growth factors. The

> induction of host cell cytokines will promote foci of

> inflammatory responses in addition to promoting

> cellular proliferation, tissue remodelling and healing

> processes that, if persistent, result in scarring.

>

> The possible role of chronic-persistent infection is

> suggested in asthmatic children where persistent

> clinical features are associated with C. pneumoniae

> infection, indicating that this infection should be

> investigated and treated in case of persistent

> asthmatic symptoms 14–15. On the other hand, in adults

> with asthma, higher titres of antibodies directed

> against C. pneumoniae are associated with more severe

> clinical disease 16. The intense neutrophil influx

> demonstrated in acute severe asthma is potentially a

> potent source of proteolytic enzymes with the ability

> to damage and activate the airway epithelium, whereas

> neutrophil elastase can cause eosinophil degranulation

> 6. The inflammatory changes caused by infection with

> C. pneumoniae have the potential to amplify the

> inflammation and airway damage present in asthma.

> Furthermore, standard asthma treatment may potentially

> enhance this response, given the ability of

> corticosteroids to reactivate C. pneumoniae infection.

> These data suggest that C. pneumoniae infection may

> influence the clinical course of asthma.

>

> In the same way, preliminary data on chronic infection

> with C. pneumoniae in patients with COPD and its

> interaction with host cells indicate that this agent

> may be implicated in the modulation of the natural

> history of chronic bronchitis and emphysema 12.

>

> The interesting finding of the study by Gieffers et

> al. 5 is the demonstration that granulocytes are one

> of the main target of C. pneumoniae infection and that

> these cells can act as " infecting " cells and reservoir

> of the pathogen. These data confirm the excellent

> capacity of C. pneumoniae to survive in different

> immune cells, use the immune cells as carriers for

> breaching the blood-tissue barriers, and potentially

> cause chronic/persistent infections.

>

> Chronic infection is probably the real challenge in

> Chlamydia pneumoniae infection and we certainly need

> new studies addressing the question whether Chlamydia

> pneumoniae long-term survival within immune and

> nonimmune cells has a role in chronic pulmonary and

> extrapulmonary diseases.

>

> References

>

>

> Neuman FJ. Chlamydia pneumoniae-atherosclerosis link:

> a sound concept in search for clinical relevance.

> Circulation 2002;106:2414–2416.[Free Full Text]

> Grimaldi LM, Pincherle A, elli-Boneschi F, et

> al. An MRI study of Chlamydia pneumoniae infection in

> Italian multiple sclerosis patients. Mult Scler

> 2003;9:467–471.[CrossRef][iSI][Medline] [Order article

> via Infotrieve]

> Blain BJ, Gerard HC, Arking EJ, et al. Identification

> and localization of Chlamydia pneumoniae in the

> Alzheimer's brain. Med Microbiol Immunol

> 1998;187:23–42.[CrossRef][iSI][Medline] [Order article

> via Infotrieve]

> Dechend R, Maass M, Gieffer J, et al. Chlamydia

> pneumoniae infection of vascular smooth muscle and

> endothelial cells activates NF-B and induces tissue

> factor and PAI-1 expression: a potential link to

> accelerated arteriosclerosis. Circulation

> 1999;100:1369–1373.[Abstract/Free Full Text]

> Gieffers J, van Zandbergen G, Rupp J, et al.

> Phagocytes transmit Chlamydia pneumoniae from the lung

> to the vasculature. Eur Respir J

> 2004;23:506–510.[Abstract/Free Full Text]

> Wark PAB, ston SL, Simpson JL, Hensley MJ, Gibson

> PG. Chlamydia pneumoniae immunoglobulin A reactivation

> and airway inflammation in acute asthma. Eur Respir J

> 2002;20:834–840.[Abstract/Free Full Text]

> Moazed TC, Kuo CC, Grayston JT, LA. Evidence

> of systemic dissemination of Chlamydia pneumoniae via

> macrophages in the mouse. J Infect Dis

> 1998;177:1322–1325.[iSI][Medline] [Order article via

> Infotrieve]

> Blasi F, Boman J, Esposito G, et al. Chlamydia

> pneumoniae DNA detection in peripheral blood

> mononuclear cells is predictive of vascular infection.

> J Infect Dis

> 1999;180:2074–2076.[CrossRef][iSI][Medline] [Order

> article via Infotrieve]

> May AE, Redecke V, Grüner S, et al. Recruitment of

> Chlamydia pneumoniae-infected macrophages to the

> carotid artery wall in noninfected, nonatherosclerotic

> mice. Arterioscler Thromb Vasc Biol

> 2003;23:789–794.[Abstract/Free Full Text]

> MacIntyre A, Abramov R, Hammond CJ, et al. Chlamydia

> pneumoniae infection promotes the transmigration of

> monocytes through human brain endothelial cells. J

> Neurosci Res 2003;71:740–750.[CrossRef][iSI][Medline]

> [Order article via Infotrieve]

> Lenz DC, Lu L, Conant SB, et al. A Chlamydia

> pneumoniae-specific peptide induces experimental

> autoimmune encephalomyelitis in rats. J Immunol

> 2001;167:1803–1808.[Abstract/Free Full Text]

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