Temporal Delay of Peak T-Cell Immunity Determines<i>Chlamydia pneumoniae</i>Pulmonary Disease in Mice

Wang, Chengming; Ginkel, Frederik W. van; Kim, Teayoun; Li, Dan; Dennis, John C.; Kaltenboeck, Bernhard

doi:10.1128/iai.00569-08

Cited by 8 publications

(6 citation statements)

References 78 publications

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“…A/J and BALB/c mice were used to generate sera against each of the nine chlamydial species. Mice were inoculated intranasally under light isoflurane anesthesia with 20-l chlamydial stocks (71). High doses of SPG-diluted chlamydiae (10 3 to 10 8 genomes/mouse) were inoculated three times at 4-to 6-week intervals to produce high-titer, high-affinity IgG antibodies against chlamydial antigens encountered during natural Chlamydia infection.…”

Section: Methodsmentioning

confidence: 99%

Defining Species-Specific Immunodominant B Cell Epitopes for Molecular Serology of Chlamydia Species

Rahman

Chowdhury

Poudel

et al. 2015

Clin. Vaccine Immunol.

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107

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bUrgently needed species-specific enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies against Chlamydia spp. have been elusive due to high cross-reactivity of chlamydial antigens. To identify Chlamydia species-specific B cell epitopes for such assays, we ranked the potential epitopes of immunodominant chlamydial proteins that are polymorphic among all Chlamydia species. High-scoring peptides were synthesized with N-terminal biotin, followed by a serine-glycine-serine-glycine spacer, immobilized onto streptavidin-coated microtiter plates, and tested with mono-specific mouse hyperimmune sera against each Chlamydia species in chemiluminescent ELISAs. For each of nine Chlamydia species, three to nine dominant polymorphic B cell epitope regions were identified on OmpA, CT618, PmpD, IncA, CT529, CT442, IncG, Omp2, TarP, and IncE proteins. Peptides corresponding to 16-to 40-amino-acid species-specific sequences of these epitopes reacted highly and with absolute specificity with homologous, but not heterologous, Chlamydia monospecies-specific sera. Host-independent reactivity of such epitopes was confirmed by testing of six C. pecorum-specific peptides from five proteins with C. pecorum-reactive sera from cattle, the natural host of C. pecorum. The probability of cross-reactivity of peptide antigens from closely related chlamydial species or strains correlated with percent sequence identity and declined to zero at <50% sequence identity. Thus, phylograms of B cell epitope regions predict the specificity of peptide antigens for rational use in the genus-, species-, or serovar-specific molecular serology of Chlamydia spp. We anticipate that these peptide antigens will improve chlamydial serology by providing easily accessible assays to nonspecialist laboratories. Our approach also lends itself to the identification of relevant epitopes of other microbial pathogens.

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Section: Methodsmentioning

confidence: 99%

Defining Species-Specific Immunodominant B Cell Epitopes for Molecular Serology of Chlamydia Species

Rahman

Chowdhury

Poudel

et al. 2015

Clin. Vaccine Immunol.

Self Cite

107

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“…Studies in animals have shown that a deficiency in the IFN-γ response, an overtly suppressive IL-10 response, or a delay in the development of a global T cell response during chlamydial infection can all lead to enhanced bacterial dissemination and disease sequelae [15] , [16] , [36] . Given these previous studies, it seems plausible that the development of anti-chlamydial Th2 immune responses could lead to increased disease susceptibility and immunopathology.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts

et al. 2011

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Chlamydiae are intracellular bacteria that commonly cause infections of the respiratory and genital tracts, which are major clinical problems. Infections are also linked to the aetiology of diseases such as asthma, emphysema and heart disease. The clinical management of infection is problematic and antibiotic resistance is emerging. Increased understanding of immune processes that are involved in both clearance and immunopathology of chlamydial infection is critical for the development of improved treatment strategies. Here, we show that IL-13 was produced in the lungs of mice rapidly after Chlamydia muridarum (Cmu) infection and promoted susceptibility to infection. Wild-type (WT) mice had increased disease severity, bacterial load and associated inflammation compared to IL-13 deficient (−/−) mice as early as 3 days post infection (p.i.). Intratracheal instillation of IL-13 enhanced bacterial load in IL-13−/− mice. There were no differences in early IFN-g and IL-10 expression between WT and IL-13−/− mice and depletion of CD4+ T cells did not affect infection in IL-13−/− mice. Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. We also showed that IL-13 deficiency increased macrophage uptake of Cmu in vitro and in vivo. Moreover, the depletion of IL-13 during infection of lung epithelial cells in vitro decreased the percentage of infected cells and reduced bacterial growth. Our results suggest that enhanced IL-13 responses in the airways, such as that found in asthmatics, may promote susceptibility to chlamydial lung infection. Importantly the role of IL-13 in regulating infection was not limited to the lung as we showed that IL-13 also promoted susceptibility to Cmu genital tract infection. Collectively our findings demonstrate that innate IL-13 release promotes infection that results in enhanced inflammation and have broad implications for the treatment of chlamydial infections and IL-13-associated diseases.

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“…L-arginine is a crucial component for both inducible nitric oxide synthase (iNOS) and ARGase ½. It has been hypothesized that the enhanced expression of host SOD2 and ARG2 protects the host cells from the damaging ROS and RNOS [85–87], and both genes were found to be up-regulated in our analyses. FABP4 (fatty acid binding protein 4) is primarily expressed in adipocytes and macrophages, and has roles in modulating immune responses and in lipid metabolism [88].…”

Section: Discussionmentioning

confidence: 71%

TLR3 Deficiency Leads to a Dysregulation in the Global Gene-Expression Profile in Murine Oviduct Epithelial Cells Infected with Chlamydia muridarum

Kumar¹,

Derbigny²

2018

Int J Microbiol Curr Res

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Chlamydia trachomatis replicates primarily in the epithelial cells lining the genital tract and induces the innate immune response by triggering cellular pathogen recognition receptors (PRRs). Our previous studies showed that Toll-like receptor 3 (TLR3) is expressed in murine oviduct epithelial (OE) cells, is the primary PRR triggered by C. muridarum (Cm) early during infection to induce IFN-β synthesis, and that TLR3 signaling regulates the chlamydial induced synthesis of a plethora of other innate inflammatory modulators including IL-6, CXCL10, CXCL16 and CCL5. We also showed that the expression of these cytokines induced by Chlamydia was severely diminished during TLR3 deficiency; however, the replication of Chlamydiain TLR3 deficient OE cells was more robust than in WT cells. These data suggested that TLR3 had a biological impact on the inflammatory response to Chlamydia infection; however, the global effects of TLR3 signaling in the cellular response to Chlamydia infection in murine OE cells has not yet been investigated. To determine the impact of TLR3 signaling on Chlamydia infection in OE cell at the transcriptome level, we infected wild-type (OE-WT) and TLR3-deficient (OE-TLR3KO) cells with Cm, and performed transcriptome analyses using microarray. Genome-wide expression and ingenuity pathway analysis (IPA) identified enhanced expression of host genes encoding for components found in multiple cellular processes encompassing: (1) pro-inflammatory, (2) cell adhesion, (3) chemoattraction, (4) cellular matrix and small molecule transport, (5) apoptosis, and (6) antigen-processing and presentation. These results support a role for TLR3 in modulating the host cellular responses to Cm infection that extend beyond inflammation and fibrosis, and shows that TLR3 could serve a potential therapeutic target for drug and/or vaccine development.

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Temporal Delay of Peak T-Cell Immunity DeterminesChlamydia pneumoniaePulmonary Disease in Mice

Cited by 8 publications

References 78 publications

Defining Species-Specific Immunodominant B Cell Epitopes for Molecular Serology of Chlamydia Species

Defining Species-Specific Immunodominant B Cell Epitopes for Molecular Serology of Chlamydia Species

Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts

TLR3 Deficiency Leads to a Dysregulation in the Global Gene-Expression Profile in Murine Oviduct Epithelial Cells Infected with Chlamydia muridarum

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