Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis.
Chlamydia pneumoniae (CP) lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chron...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3808399?pdf=render |
id |
doaj-57fb2d28ecfb4ec4a9f3d685dfce98b5 |
---|---|
record_format |
Article |
spelling |
doaj-57fb2d28ecfb4ec4a9f3d685dfce98b52020-11-25T02:25:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7744710.1371/journal.pone.0077447Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis.Madhulika JupelliKenichi ShimadaNorika ChibaAnatoly SlepenkinRanda AlsabehHeather D JonesEllena PetersonShuang ChenMoshe ArditiTimothy R CrotherChlamydia pneumoniae (CP) lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5) CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs). Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.http://europepmc.org/articles/PMC3808399?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Madhulika Jupelli Kenichi Shimada Norika Chiba Anatoly Slepenkin Randa Alsabeh Heather D Jones Ellena Peterson Shuang Chen Moshe Arditi Timothy R Crother |
spellingShingle |
Madhulika Jupelli Kenichi Shimada Norika Chiba Anatoly Slepenkin Randa Alsabeh Heather D Jones Ellena Peterson Shuang Chen Moshe Arditi Timothy R Crother Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. PLoS ONE |
author_facet |
Madhulika Jupelli Kenichi Shimada Norika Chiba Anatoly Slepenkin Randa Alsabeh Heather D Jones Ellena Peterson Shuang Chen Moshe Arditi Timothy R Crother |
author_sort |
Madhulika Jupelli |
title |
Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. |
title_short |
Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. |
title_full |
Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. |
title_fullStr |
Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. |
title_full_unstemmed |
Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis. |
title_sort |
chlamydia pneumoniae infection in mice induces chronic lung inflammation, ibalt formation, and fibrosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Chlamydia pneumoniae (CP) lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5) CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs). Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis. |
url |
http://europepmc.org/articles/PMC3808399?pdf=render |
work_keys_str_mv |
AT madhulikajupelli chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT kenichishimada chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT norikachiba chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT anatolyslepenkin chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT randaalsabeh chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT heatherdjones chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT ellenapeterson chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT shuangchen chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT moshearditi chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis AT timothyrcrother chlamydiapneumoniaeinfectioninmiceinduceschroniclunginflammationibaltformationandfibrosis |
_version_ |
1724852958544265216 |