Gene expression profiles of early pneumococcal otitis media in the rat

Chen, Anton; Li, Ha-Sheng; Hebda, Patricia A.; Zeevi, A.; Swarts, J. Douglas

doi:10.1016/j.ijporl.2005.03.033

Cited by 14 publications

(11 citation statements)

References 53 publications

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“…For the host, the response tends to be focused on clearing the pathogen, mediated by the activation of innate and adaptive defense mechanisms. A few studies have attempted to characterize the host response to pneumococci, using both in vitro and in vivo models of infection (11,12,30,37,44). In this study, we examined the global transcriptional response of human epithelial cells to pneumococcal adherence in vitro, in particular in relation to the pneumococcal capsule.…”

Section: Discussionmentioning

confidence: 99%

“…In a human monocytic cell line, the expression of IL-8, but not IL-1␤, was found to be induced after 3 h of exposure to pneumococci (44), while IL-1␤ and IL-6 production was observed in monocytes after 24 h of exposure (10). In vivo, IL-1␤ and MIP-2ab were induced during early pneumococcal otitis media in rats (11), while AP-1 family transcription factors were induced both early and late during otitis media (11,30).…”

Section: Discussionmentioning

confidence: 99%

“…They identified 40 genes that were responsive independent of pneumolysin and 142 pneumolysin-responsive genes, including those encoding IL-8, MIP-1␤, lysozyme, and caspases 4 and 6 (44). The examination of gene expression profiles for the middle ears of rats during early and late stages of S. pneumoniaeinduced otitis media identified transient expression of cytokines and persistent upregulation of several transcription factors, including c-Jun and c-myc (11,30). Similarly, transcriptional profiling of the cortex and hippocampus of rats during acute pneumococcal meningitis identified 598 differentially regulated genes, associated mainly with growth control, signal transduction, cell death/survival, the cytoskeleton, and innate and adaptive immunity (12).…”

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confidence: 99%

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Analysis of the In Vitro Transcriptional Response of Human Pharyngeal Epithelial Cells to AdherentStreptococcus pneumoniae: Evidence for a Distinct Response to Encapsulated Strains

2007

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Infection of the human host by Streptococcus pneumoniae begins with colonization of the nasopharynx, which is mediated by the adherence of bacteria to the respiratory epithelium. Several studies have indicated an important role for the pneumococcal capsule in this process. Here, we used microarrays to characterize the in vitro transcriptional response of human pharyngeal epithelial Detroit 562 cells to the adherence of serotype 2 encapsulated strain D39, serotype 19F encapsulated strain G54, serotype 4 encapsulated strain TIGR4, and their nonencapsulated derivatives (⌬cps). In total, 322 genes were found to be upregulated in response to adherent pneumococci. Twenty-two genes were commonly induced, including those encoding several cytokines (e.g., interleukin 1␤ [IL-1␤] and IL-6), chemokines (e.g., IL-8 and CXCL1/2), and transcriptional regulators (e.g., FOS), consistent with an innate immune response mediated by Toll-like receptor signaling. Interestingly, 85% of genes were induced specifically by one or more encapsulated strains, suggestive of a capsule-dependent response. Importantly, purified capsular polysaccharides alone had no effect. Over a third of these loci encoded products predicted to be involved in transcriptional regulation and signal transduction, in particular mitogenactivated protein kinase signaling pathways. Real-time PCR of a subset of 10 genes confirmed the microarray data and showed a time-dependent upregulation of, especially, innate immunity genes. The downregulation of epithelial genes was most pronounced upon adherence of D39⌬cps, as 68% of the 161 genes identified were repressed only by this nonencapsulated strain. In conclusion, we identified a subset of host genes specifically induced by encapsulated strains during in vitro adherence and have demonstrated the complexity of interactions occurring during the initial stages of pneumococcal infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Analysis of the In Vitro Transcriptional Response of Human Pharyngeal Epithelial Cells to AdherentStreptococcus pneumoniae: Evidence for a Distinct Response to Encapsulated Strains

2007

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“…Host gene-expression changes in an infection model have been investigated in a rat model of otitis media (Chen et al, 2005). Twelve hours following pneumococcal challenge, 280 genes in the middle ear (effusion and mucosa) showed a greater than twofold change in expression compared with mock-infected controls.…”

Section: Global Analysis Of Host Responsesmentioning

confidence: 99%

“…For example, it has been found that the transcription factor fra-1, implicated in bone proliferation, is upregulated during experimental otitis media. This provides a candidate mechanism to explain clinical features of otitis media involving the bone that are seen in both human patients and animals (Chen et al, 2005). The global response to nasopharyngeal colonization has also been investigated in a mouse model .…”

Section: Global Analysis Of Host Responsesmentioning

confidence: 99%

Innate immunity and the pneumococcus

Paterson

Mitchell

2006

Microbiology

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The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).

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