Toll-like Receptor 2-independent Host Innate Immune Response Against an Epidemic Strain of Streptococcus suis that Causes a Toxic Shock-Like Syndrome in Humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Claude Lachance
PROVIDER: E-GEOD-45863 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Streptococcus suis is an emerging zoonotic agent causing meningitis and septicemia. Outbreaks in humans in China with atypical cases of streptococcal toxic shock-like syndrome have been described to be caused by a clonal epidemic S. suis strain characterized as sequence type (ST) 7 by multilocus sequence typing, different from the classical ST1 usually isolated in Europe. Previous in vitro studies showed that Toll-like receptor (TLR) 2 plays a major role in S. suis ST1 interactions with host cells. In the present study, the in vivo role of TLR2 in systemic infections caused by S. suis ST1 or ST7 strains using TLR2 deficient (TLR2-/-) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2-/- mice remained unaffected when compared to wild type (WT) mice. The lack of mortality could not be associated with a lower bacterial burden; however, a significant decrease in the induction of pro-inflammatory mediators, as evaluated by microarray, real-time PCR and protein assays, was observed. On the other hand, TLR2-/- mice infected with the epidemic ST7 strain presented no significant differences regarding survival and expression of pro-inflammatory mediators when compared to the WT mice. Together, these results show a TLR2-independent host innate immune response to S. suis that depends on the strain. Total RNA obtained from spleen of C57BL/6 mice or C57BL/6 TLR2-KO mice infected with Streptococcus suis strain P1/7. Four replicates in both groups.
2013-06-01 | E-GEOD-45861 | biostudies-arrayexpress
Project description:Streptococcus suis is an emerging zoonotic agent causing meningitis and septicemia. Outbreaks in humans in China with atypical cases of streptococcal toxic shock-like syndrome have been described to be caused by a clonal epidemic S. suis strain characterized as sequence type (ST) 7 by multilocus sequence typing, different from the classical ST1 usually isolated in Europe. Previous in vitro studies showed that Toll-like receptor (TLR) 2 plays a major role in S. suis ST1 interactions with host cells. In the present study, the in vivo role of TLR2 in systemic infections caused by S. suis ST1 or ST7 strains using TLR2 deficient (TLR2-/-) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2-/- mice remained unaffected when compared to wild type (WT) mice. The lack of mortality could not be associated with a lower bacterial burden; however, a significant decrease in the induction of pro-inflammatory mediators, as evaluated by microarray, real-time PCR and protein assays, was observed. On the other hand, TLR2-/- mice infected with the epidemic ST7 strain presented no significant differences regarding survival and expression of pro-inflammatory mediators when compared to the WT mice. Together, these results show a TLR2-independent host innate immune response to S. suis that depends on the strain. Total RNA obtained from spleen of C57BL/6 mice or C57BL/6 TLR2-KO mice infected with Streptococcus suis strain SC84. Four replicates in both groups.
2013-06-01 | E-GEOD-45862 | biostudies-arrayexpress
Project description:Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFNM-NM-3 was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFNM-NM-3-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFNM-NM-3 in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China. Total RNA obtained from spleen of C57BL/6 mice infected with Streptococcus suis strain 89-1591 or mock-infected with THB. Four replicates in both groups.
2013-03-27 | E-GEOD-41520 | biostudies-arrayexpress
Project description:Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFNM-NM-3 was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFNM-NM-3-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFNM-NM-3 in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China. Total RNA obtained from spleen of C57BL/6 mice infected with Streptococcus suis strain P1/7 or mock-infected with THB. Four replicates in both groups.
2013-03-27 | E-GEOD-41521 | biostudies-arrayexpress
Project description:Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFNM-NM-3 was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFNM-NM-3-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFNM-NM-3 in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China. Total RNA obtained from spleen of C57BL/6 mice infected with Streptococcus suis strain SC84 or mock-infected with THB. Four replicates in both groups.
2013-03-27 | E-GEOD-41522 | biostudies-arrayexpress
Project description:Streptococcus suis serotype 2 is an important pathogen of pigs, and the disease it causes is characterized by meningitis, septicaemia and pneumonia with high mortality. The pathogen is also an emerging zoonotic agent and threatens humans that are exposed to pigs or their by-products. We investigated the response of PBMC (Peripheral Blood Mononuclear Cell), brain and lung tissues to infection with S. suis 2 strain SC19 by using the Affymetrix Porcine Genome Array. Six piglets free of S. suis 2 were allocated randomly to the infected group and the uninfected group. Each piglet of the infected group was intravenous injection with Streptococcus suis 2 strain SC19 at a dose of 3Ã105 colony-forming units (CFU). Each piglet of the noninfected group was treated similarly with an identical volume of PBS as control. At 24 h after challenge, the pigs were slaughtered and their brains, lungs and PBMC were collected with RNase-free equipment for microarray analysis.
2010-10-26 | E-GEOD-24889 | biostudies-arrayexpress
Project description:Microglia are the resident mononuclear phagocytes of the CNS parenchyma and represent an initial line of defense against invading microorganisms. Microglia utilize Toll-like receptors (TLRs) for pathogen recognition and TLR2 specifically senses conserved motifs of gram-positive bacteria including lipoproteins, lipoteichoic acids, and peptidoglycan (PGN) leading to cytokine/chemokine production. Interestingly, primary microglia derived from TLR2 knockout (KO) mice over-expressed numerous IL-12 family members, including IL-12p40, IL-12p70, and IL-27 in response to intact S. aureus, but not the less structurally complex TLR2 ligands Pam3CSK4 or PGN. The ability of intact bacteria to augment IL-12 family member expression was specific for gram-positive organisms, since numerous gram-negative strains were unable to elicit exaggerated responses in TLR2 KO microglia. Inhibition of SYK or IRAK4 signaling did not impact heightened IL-12 family member production in S. aureus-treated TLR2 KO microglia, whereas PI3K, MAPK, and JNK inhibitors were all capable of restoring exaggerated cytokine expression to wild type levels. Additionally, elevated IL-12 production in TLR2 KO microglia was ablated by a TLR9 antagonist, suggesting that TLR9 drives IL-12 family member production following exposure to intact bacteria that remains unchecked in the absence of TLR2 signaling. Collectively, these findings indicate crosstalk between TLR2 and TLR9 pathways to regulate IL-12 family member production by microglia. The summation of TLR signals must be tightly controlled to ensure the timely cessation and/or fine tuning of cytokine signaling to avoid nonspecific bystander damage due to sustained IL-12 release. TLR2 KO mice were backcrossed with C57BL/6 animals for a minimum of eight generations prior to use in these studies. Age- and sex-matched C57BL/6 mice were used as wild type (WT) controls. Primary mixed glial cultures were prepared from the cerebral corticies of neonatal mice (2-4 days of age) and microglia were harvested using a differential shaking technique with a purity of >98%. A USA300 community-acquired methicillin-resistant S. aureus (CA-MRSA) clinical isolate recovered from a patient with a fatal brain abscess was used to stimulate the microglia isolates. Bacterial strains were heat-inactivated and used to stimulate microglia at 107 colony forming units (cfu)/well for 6 and 12 hours time points. Three replicates of each mouse type (WT, TLR2 KO) at both time points 6 and 12 hours were used for the microarray experiments. Data was only usable for 2 replicates of the KO-12 hr group.
2014-12-22 | E-GEOD-24935 | biostudies-arrayexpress
Project description:Streptococcus suis is an important emerging worldwide pig pathogen and zoonotic agent with rapid evolution of virulence and drug resistance. Licochalcone A, used in traditional Chinese medicine, exhibits antimicrobial, antioxidant and anti-inflammatory activities. Herein, a whole-genome DNA microarray was used to investigate the global transcriptional regulation of Streptococcus suis 05ZYH33 treated by subinhibitory concentration of licochalcone A. 132 genes were differentially regulated upon liochalcone A treatment, including 78 genes up-regulated and 54 genes down-regulated which included many central biological functions such as metabolism, transcription and translation. We tried to investigate the antimicrobial mechanism of licochalcone A in the aspect of bacterial cell cycle control. Our analysis indicated that licochalcone A might inhibit the growth of S. suis by controlling the replication initiation and cell division through amino acid metabolism. A cDNA microarray imprinted with 2156 genes representing about 98% of Streptococcus suis serotype 2 genome was used for transcriptome analysis. For two-sample (reference vs. test) microarray hybridization, four independent bacterial cultures from each condition were prepared as biological replicates for RNA isolation. Four dual-fluorescence-labeled cDNA probes were prepared to hybridize with four slides, respectively. Pairwise comparisons were made using dye swaps to avoid labeling bias. A ratio of mRNA levels (test/reference) was calculated for each gene. Significant changes of gene expression were identified with the SAM software. After the SAM analysis, only genes with at least 2-fold changes in expression were collected for further analysis.
2013-05-07 | E-GEOD-46666 | biostudies-arrayexpress
Project description:Comparative genome hybridization was used to study genomic diversity among S. suis strains in more detail. All strains were hybridized to an oligo-array based on the genome of P1/7 with P1/7 as an internal reference in all experiments.
2010-12-31 | E-MEXP-2531 | biostudies-arrayexpress
Project description:Comparative genome hybridization was used to study genomic diversity among S. suis strains in more detail. All strains were hybridized to an oligo-array based on the genome of P1/7 with P1/7 as an internal reference in all experiments.
2010-12-31 | E-MEXP-2533 | biostudies-arrayexpress