Fate of Chlamydophila pneumoniae in human monocyte-derived dendritic cells: Long lasting infection

Wittkop, Ulrike; Krausse-Opatz, Birgit; Gust, Tatjana C; Kirsch, Torsten; Hollweg, Günther; Köhler, Lars; Zenke, Martin; Gérard, Hervé C.; Hudson, Alan P.; Zeidler, Henning; Wagner, Annette D.

doi:10.1016/j.micpath.2005.11.006

Cited by 14 publications

(23 citation statements)

References 49 publications

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“…Furthermore, we demonstrated the production of tumor necrosis factor (TNF)‐α by DCs in temporal artery biopsies of GCA patients (Wagner et al , 2003). We have also shown that C. pneumoniae is able to infect DCs persistently over weeks, with marked production of TNF‐α during the first days of infection (Wittkop et al , 2006).…”

Section: Introductionmentioning

confidence: 91%

In vitroneutralization of tumor necrosis factor-Î± duringChlamydia pneumoniaeinfection impairs dendritic cells maturation/function and increases chlamydial progeny

Njau

Wittkop

Rohde

et al. 2009

FEMS Immunology &Amp; Medical Microbiology

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Dendritic cells (DCs) produce tumor necrosis factor (TNF)-alpha upon infection and contribute in various ways to defense against pathogenic agents. Several biological agents have been designed to inhibit TNF-alpha activity. However, the use of these inhibitors has been associated with an increased rate of certain opportunistic infections. To study the effect of TNF-alpha inhibition, human monocyte-derived DCs were infected with Chlamydia pneumoniae. TNF-alpha was neutralized by adalimumab, a human anti-TNF-alpha monoclonal antibody. Chlamydiae induced the maturation of DC as determined by flow cytometry and quantitative real-time PCR. However, DC maturation was impaired in the presence of adalimumab. Moreover, neutralization of TNF-alpha resulted in a significant increase of infectious progeny, 16S rRNA gene copy number and development of larger inclusions consisting of different stages of chlamydial development. Additionally, chlamydial infection induced secretion of cytokines/chemokines, which were downregulated by adalimumab treatment. Our data reveal an indirect effect on maturation of DC by C. pneumoniae and that maturation is crucial for the restriction of chlamydial development. The results also demonstrate an increase in infectious progeny after TNF-alpha inhibition, suggesting a contribution of TNF-alpha produced by DCs to chlamydial growth arrest. These data suggest a possible mechanism by which TNF-alpha inhibition enhances the risk of intracellular infections.

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Section: Introductionmentioning

confidence: 91%

In vitroneutralization of tumor necrosis factor-Î± duringChlamydia pneumoniaeinfection impairs dendritic cells maturation/function and increases chlamydial progeny

Njau

Wittkop

Rohde

et al. 2009

FEMS Immunology &Amp; Medical Microbiology

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“…The mDCs generated during C. pneumoniae infections in one report are functionally suppressive. The mDCs disseminate the pathogen and drive immunosuppressive T cell stimulation (Wittkop et al, 2006). Viruses (e.g., hepatitis C virus, HCV) can also infect mDCs and expand suppressive immune responses, typically through Th-17 response (Fang et al, 2013).…”

Section: Correlation Of Microbial and Non-microbial Factors With Flucmentioning

confidence: 99%

“…Mucosal pathogens HCV (Goutagny et al, 2003), C. pneumoniae (Wittkop et al, 2006), HIV (Gougeon et al, 2012), and M. tuberculosis (Chackerian et al, 2002), among others, survive and replicate within DCs. Interestingly, many of these pathogens are found to be disseminated to distant sites within the host and thought to have a role in inflammatory disease (Bobryshev et al, 2004).…”

Section: Blood Mdcs As Carriers Of Infectionmentioning

confidence: 99%

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

et al. 2014

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The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g., cancer). Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDCs) in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of dendritic cell homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome) and activation state of these mDCs. These may provide important clues (“the canary in the coal mine”) of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia.

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“…DCs were isolated from monocytes purified from PBMC by negative selection using the magnetic column separation system (StemCell Technologies, Inc.) as previously described [30]. Briefly, purified monocytes were cultured in RPMI 1640 medium supplemented with 10% FCS, 5% L-glutamine, Hepes, 5% sodium pyruvate, 5% antibiotics, GM-CSF (100 ng/mL) and IL-4 (50 ng/mL) and set up in 24-well tissue culture plates at 5×10 5 /mL.…”

Section: Methodsmentioning

confidence: 99%

Luminal-Applied Flagellin Is Internalized by Polarized Intestinal Epithelial Cells and Elicits Immune Responses via the TLR5 Dependent Mechanism

Eaves-Pyles

Tan

et al. 2011

PLoS ONE

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Bacteria release flagellin that elicits innate responses via Toll-like receptor 5 (TLR5). Here, we investigated the fate of apically administrated full length flagellin from virulent and avirulent bacteria, along with truncated recombinant flagellin proteins in intestinal epithelial cells and cellular responses. Flagellin was internalized by intestinal epithelial cell (IEC) monolayers of IEC-18. Additionally, apically applied flagellin was internalized by polarized human Caco-2BBe and T-84 cells in a TLR5 dependent mechanism. More, flagellin exposure did not affect the integrity of intestinal monolayers. With immunofluorescent staining, internalized flagellin was detected in both early endosomes as well as lysosomes. We found that apical exposure of polarized Caco-2BBe and T-84 to flagellin from purified Salmonella, Escherichia coli O83:H1 (isolate from Crohn’s lesion) or avirulent E. coli K12 induced comparable levels of basolateral IL-8 secretion. A recombinant protein representing the conserved amino (N) and carboxyl (C) domains (D) of the flagellin protein (ND1/2ECHCD2/1) induced IL-8 secretion from IEC similar to levels elicited by full-length flagellins. However, a recombinant flagellin protein containing only the D3 hypervariable region elicited no IL-8 secretion in both cell lines compared to un-stimulated controls. Silencing or blocking TLR5 in Caco-2BBe cells resulted in a lack of flagellin internalization and decreased IL-8 secretion. Furthermore, apical exposure to flagellin stimulated transepithelial migration of neutrophils and dendritic cells. The novel findings in this study show that luminal-applied flagellin is internalized by normal IEC via TLR5 and co-localizes to endosomal and lysosomal compartments where it is likely degraded as flagellin was not detected on the basolateral side of IEC cultures.

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Fate of Chlamydophila pneumoniae in human monocyte-derived dendritic cells: Long lasting infection

Cited by 14 publications

References 49 publications

In vitroneutralization of tumor necrosis factor-Î± duringChlamydia pneumoniaeinfection impairs dendritic cells maturation/function and increases chlamydial progeny

In vitroneutralization of tumor necrosis factor-Î± duringChlamydia pneumoniaeinfection impairs dendritic cells maturation/function and increases chlamydial progeny

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

Luminal-Applied Flagellin Is Internalized by Polarized Intestinal Epithelial Cells and Elicits Immune Responses via the TLR5 Dependent Mechanism

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