Ion of secreted components [20]. Thus,we hypothesize that different bacterial components, especially differences in lipoproteins (secreted or not) present in typical S. suis strains and those from the epidemic S. suis ST7 strain may varyTLR2-Independent Activation by S. suisand play a distinct role on cell activation and in the pathogenesis of the systemic inflammatory disease caused by this pathogen. Results obtained in the present study with both ST1 and ST7 strains reinforce the concept of multiple Gram-positive cell receptors. Further investigations using different genetic mouse models defective in single TLRs, MyD88 or with double TLR deletions will help clarify the role of other receptors in the innate recognition of typical ST1 S. suis strains but mainly, the epidemic S. suis ST7 strain. Results obtained in this study can be applied to the acute systemic infection caused by S. suis. However, S. suis is also able to induce meningitis in a mouse model of infection at later incubation times (between 5 and 14 days post-infection) [12]. Some cases of meningitis have also been induced in humans by the ST7 strain during the outbreak in China [22]. In fact, the actual in vivo role of TLR2 in meningitis caused by any strain of S. suis is unknown, and it would be difficult to predict. For example, it has been reported that TLR2 does not play a major role in Streptococcus pneumoniae killing and disease after either systemic disease or pneumonia [37,38]. However, other studies showed that TLR22/2 mice are significantly more affected and have increased bacterial loads than WT mice in experimental meningitis [39,40]. Although TLR2 has been suggested to be implicated in S. suis meningitis [41], further in vivo studies with TLR22/2 mice are warranted.In summary, results obtained in this study reveal that infection of mice by highly pathogenic strains of S. suis may follow TLR2dependent or independent pathways depending on the strain. The atypical epidemic ST7 strain, responsible for STSLS human cases, would not only induce a massive and distinctive IFN-c response but also activate cells using currently unknown receptors which are different from those activated by highly virulent ST1 strains.Supporting InformationGenes upregulated greater than three-fold in wild type C57BL/6 (B6) or TLR22/2 mice infected with either S. suis P1/7 (ST1) strain or epidemic SC84 (ST7) strain for 6 h. (DOCX)Table SAcknowledgmentsWe would like to thank Sonia Lacouture for BIBS39 site invaluable technical assistance.Author ContributionsConceived and designed the experiments: CL MS MG. Performed the experiments: CL PPG. Analyzed the data: CL PPG. Contributed reagents/ ML-281 biological activity materials/analysis tools: JX MG. Wrote the paper: CL MS MG.
Uterine cancer is the most commonly diagnosed gynecologic malignancy in the United States and is the eighth leading cause of death from cancer among American women [1]. Endometrial cancers (ECs) account for the vast majority of uterine cancers. Endometrioid, serous, and clear cell carcinomas represent the three major histological subtypes of EC. Each subtype arises from distinct precursor lesions, has distinct clinical behaviors and distinct molecular etiologies [2], [3].Endometrioid ECs (EECs) are estrogen-dependent tumors associated with an overall favorable prognosis evidenced by a 5year relative survival rate of ,90 [4]. In contrast, serous and clear cell ECs (non-endometrioid ECs (NEECs)) are clinically aggressive, estrogen-independent tumors with 5-year.Ion of secreted components [20]. Thus,we hypothesize that different bacterial components, especially differences in lipoproteins (secreted or not) present in typical S. suis strains and those from the epidemic S. suis ST7 strain may varyTLR2-Independent Activation by S. suisand play a distinct role on cell activation and in the pathogenesis of the systemic inflammatory disease caused by this pathogen. Results obtained in the present study with both ST1 and ST7 strains reinforce the concept of multiple Gram-positive cell receptors. Further investigations using different genetic mouse models defective in single TLRs, MyD88 or with double TLR deletions will help clarify the role of other receptors in the innate recognition of typical ST1 S. suis strains but mainly, the epidemic S. suis ST7 strain. Results obtained in this study can be applied to the acute systemic infection caused by S. suis. However, S. suis is also able to induce meningitis in a mouse model of infection at later incubation times (between 5 and 14 days post-infection) [12]. Some cases of meningitis have also been induced in humans by the ST7 strain during the outbreak in China [22]. In fact, the actual in vivo role of TLR2 in meningitis caused by any strain of S. suis is unknown, and it would be difficult to predict. For example, it has been reported that TLR2 does not play a major role in Streptococcus pneumoniae killing and disease after either systemic disease or pneumonia [37,38]. However, other studies showed that TLR22/2 mice are significantly more affected and have increased bacterial loads than WT mice in experimental meningitis [39,40]. Although TLR2 has been suggested to be implicated in S. suis meningitis [41], further in vivo studies with TLR22/2 mice are warranted.In summary, results obtained in this study reveal that infection of mice by highly pathogenic strains of S. suis may follow TLR2dependent or independent pathways depending on the strain. The atypical epidemic ST7 strain, responsible for STSLS human cases, would not only induce a massive and distinctive IFN-c response but also activate cells using currently unknown receptors which are different from those activated by highly virulent ST1 strains.Supporting InformationGenes upregulated greater than three-fold in wild type C57BL/6 (B6) or TLR22/2 mice infected with either S. suis P1/7 (ST1) strain or epidemic SC84 (ST7) strain for 6 h. (DOCX)Table SAcknowledgmentsWe would like to thank Sonia Lacouture for invaluable technical assistance.Author ContributionsConceived and designed the experiments: CL MS MG. Performed the experiments: CL PPG. Analyzed the data: CL PPG. Contributed reagents/ materials/analysis tools: JX MG. Wrote the paper: CL MS MG.
Uterine cancer is the most commonly diagnosed gynecologic malignancy in the United States and is the eighth leading cause of death from cancer among American women [1]. Endometrial cancers (ECs) account for the vast majority of uterine cancers. Endometrioid, serous, and clear cell carcinomas represent the three major histological subtypes of EC. Each subtype arises from distinct precursor lesions, has distinct clinical behaviors and distinct molecular etiologies [2], [3].Endometrioid ECs (EECs) are estrogen-dependent tumors associated with an overall favorable prognosis evidenced by a 5year relative survival rate of ,90 [4]. In contrast, serous and clear cell ECs (non-endometrioid ECs (NEECs)) are clinically aggressive, estrogen-independent tumors with 5-year.
