Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells

Al-Younes, Hesham M.; Rudel, Thomas; Meyer, Thomas F.

doi:10.1046/j.1462-5822.1999.00024.x

Cited by 65 publications

(72 citation statements)

References 48 publications

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“…How C. pneumoniae persists in PMN is unknown to date. In epithelial cells, in which C. pneumoniae forms large inclusions within 48 -72 h, inclusions avoid fusion with late endosomes and lysosomes, but accumulate early transferrin receptor-positive endosomes (23). In human monocytes, however, C. pneumoniae-containing inclusions are small and characterized by large atypical RBs (24), which may be explained by the finding that in the case of infection with Chlamydia psittaci, early vacuoles fused with lysosomes in the monocytic cell line THP1 (25).…”

Section: Figure 5 Depletion Of Gr1mentioning

confidence: 99%

Polymorphonuclear Neutrophils Improve Replication ofChlamydia pneumoniaeIn Vivo upon MyD88-Dependent Attraction

Rodríguez

Fend

Jennen

et al. 2005

The Journal of Immunology

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Chlamydia pneumoniae, an obligate intracellular bacterium, causes pneumonia in humans and mice. In this study, we show that GR1+/CD45+ polymorphonuclear neutrophils (PMN) surprisingly increase the bacterial load of C. pneumoniae in vivo. Upon intranasal infection of wild-type mice, the lung weight is increased; the cytokines TNF, IL-12p40, and IFN-γ, as well as the chemokines keratinocyte-derived chemokine, MCP-1, and MIP-2 are secreted; and GR1+/CD45+ PMN are recruited into lungs 3 days postinfection. In contrast, in infected MyD88-deficient mice, which lack a key adaptor molecule in the signaling cascade of TLRs and IL-1R family members, the increase of the lung weight is attenuated, and from the analyzed cyto- and chemokines, only IL-12p40 is detectable. Upon infection, almost no influx of inflammatory cells into lungs of MyD88-deficient mice can be observed. Six days postinfection, however, MyD88-deficient mice were able to produce TNF, IFN-γ, keratinocyte-derived chemokine, and MCP-1 in amounts similar to wild-type mice, but failed to secrete IL-12p40 and MIP-2. At this time point, the infection increased the lung weight to a level similar to wild-type mice. Curiously, the chlamydial burden in MyD88-deficient mice 3 days postinfection is lower than in wild-type mice, a finding that can be reproduced in wild-type mice by depletion of GR1+ cells. In analyzing how PMN influence the chlamydial burden in vivo, we find that PMN are infected and enhance the replication of C. pneumoniae in epithelial cells. Thus, the lower chlamydial burden in MyD88-deficient mice can be explained by the failure to recruit PMN.

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Section: Figure 5 Depletion Of Gr1mentioning

confidence: 99%

Polymorphonuclear Neutrophils Improve Replication ofChlamydia pneumoniaeIn Vivo upon MyD88-Dependent Attraction

Rodríguez

Fend

Jennen

et al. 2005

The Journal of Immunology

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“…These interactions are needed to acquire nutrients, avoid fusion with lysosomes, obtain membrane components from Golgi-derived exocytic vesicles, and modify host cell functions (56,57). The chlamydial products that control these processes are thought to be proteins translocated through or inserted into the inclusion membrane via a type III secretion apparatus (58).…”

Section: Development Of Vaccines That Induce Cd8mentioning

confidence: 99%

MultipleChlamydia pneumoniaeAntigens Prime CD8+ Tc1 Responses That Inhibit Intracellular Growth of This Vacuolar Pathogen

Wizel

Starcher²,

Samten

et al. 2002

The Journal of Immunology

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CD8+ T cells play an essential role in immunity to Chlamydia pneumoniae (Cpn). However, the target Ags recognized by Cpn-specific CD8+ T cells have not been identified, and the mechanisms by which this T cell subset contributes to protection remain unknown. In this work we demonstrate that Cpn infection primes a pathogen-specific CD8+ T cell response in mice. Eighteen H-2b binding peptides representing sequences from 12 Cpn Ags sensitized target cells for MHC class I-restricted lysis by CD8+ CTL generated from the spleens and lungs of infected mice. Peptide-specific IFN-γ-secreting CD8+ T cells were present in local and systemic compartments after primary infection, and these cells expanded after pathogen re-exposure. CD8+ T cell lines to the 18 Cpn epitope-bearing peptides were cytotoxic, displayed a memory phenotype, and secreted IFN-γ and TNF-α, but not IL-4. These CTL lines lysed Cpn-infected macrophages, and the lytic activity was inhibited by brefeldin A, indicating endogenous processing of CTL Ags. Finally, Cpn peptide-specific CD8+ CTL suppressed chlamydial growth in vitro by direct lysis of infected cells and by secretion of IFN-γ and other soluble factors. These studies provide information on the mechanisms by which CD8+ CTL protect against Cpn, furnish the tools to investigate their possible role in immunopathology, and lay the foundation for future work to develop vaccines against acute and chronic Cpn infections.

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“…Third, the chlamydial inclusion appears to avoid fusion with other intracellular vesicles [16]. Thus, TLReven if they are expressed intracellularly by infected epithelial cells -may be unable to get access to the intracellular bacteria, because they are not integrated into the inclusion membrane.…”

Section: Introductionmentioning

confidence: 99%

Differential involvement of TLR2 and TLR4 in host survival during pulmonary infection with Chlamydia pneumoniae

Rodríguez

Wantia

Fend³

et al. 2006

Eur J Immunol

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The relevance of TLR2 and TLR4 for recognizing Chlamydia pneumoniae in vivo during pulmonary infection and to survive the infection was explored. We found that early immune responses triggered by C. pneumoniae partially depended on TLR2, but not on TLR4. The chemokines MIP-2 and MIP-1a were not induced, while IL-12p40 levels were higher in TLR2 -/-mice compared to wild-type mice. Secretion of TNF, keratinocytederived chemokine and monocyte chemoattractant protein-1 was attenuated in TLR2 -/-mice, while IFN-c was increased as in wild-type mice. The pulmonary cyto-and chemokine response of TLR2 -/-ÂTLR4 d/d was similar to TLR2 -/-mice. TLR2 -/-and TLR2 -/-ÂTLR4 d/d mice also attracted fewer polymorphonuclear neutrophils into the lung, while TLR4 d/d mice recruited them. Attenuated recruitment of polymorphonuclear neutrophils correlated with reduced weight loss in TLR2 -/-and TLR2 -/-ÂTLR4 d/d mice and a lower chlamydial burden 3 days post infection. At 9 days post infection, TLR2 -/-and TLR2 -/-ÂTLR4 d/d mice produced cyto-and chemokines as efficiently as wild-type mice, indicating that the involvement of TLR in inflammation varies over time. All TLR2 -/-ÂTLR4 d/d mice succumbed to the infection, while about 50% of TLR2 -/-mice died. Taken together, the function of TLR2 and TLR4 is required to survive pulmonary infection with C. pneumoniae.

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Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells

Cited by 65 publications

References 48 publications

Polymorphonuclear Neutrophils Improve Replication ofChlamydia pneumoniaeIn Vivo upon MyD88-Dependent Attraction

Polymorphonuclear Neutrophils Improve Replication ofChlamydia pneumoniaeIn Vivo upon MyD88-Dependent Attraction

MultipleChlamydia pneumoniaeAntigens Prime CD8+ Tc1 Responses That Inhibit Intracellular Growth of This Vacuolar Pathogen

Differential involvement of TLR2 and TLR4 in host survival during pulmonary infection with Chlamydia pneumoniae

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