Pment in mice although also B. burgdorferi strains that express DbpA

Pment in mice although also B. burgdorferi strains that express DbpA or B alone, or the strain that is DbpA/B deficient, are able to colonize mouse joints. The progression of the joint manifestations in dbpAB/dbpAB infected mice is biphasic with peaks at 4 and 9?1 weeks of infection, and with histologically evident arthritis at 15 weeks of infection. The most important finding of the present study is the absence of post treatment borrelial DNA persistence in the RG1662 web joints of mice infected with DbpA/B deficient B. burgdorferi, while in the mice infected DbpA and B expressing B. burgdorferi, all joint samples were borrelial DNA positive up to 12 weeks after the treatment. One obvious explanation for this phenomenon is that DbpA and B assist the bacteria in invasion to decorin rich foci in mouse joints, which in turn allows evasion of antibiotic treatment and leads to post-treatment persistence of bacterial remnants in mouse joints. Based on the results of our anti-TNF-alpha immunosuppression experiments, the nature of the persisting material in the antibiotic treated mice appears to be non-cultivable bacterial remnants. The finding that only B. burgdorferi with a particular set of adhesins can form deposits of persisting remnants after treatment is thought provoking. We and others have shown that DbpA and B molecules of different B. burgdorferi sensu lato genospecies have different abilities to mediate binding to decorin and to decorin expressing cells [22, 26, 32]. Therefore, we will next focus on evaluating the contribution of DbpA and B of different B. burgdorferi sensu lato genospecies to dissemination of the infection, to arthritis development and to the post treatment persistence potential.Supporting InformationS1 Fig. IgG antibodies against C6, DbpA and DbpB in mouse serum samples. Antibody levels were measured using enzyme immunoassays with C6 peptide (A and D), DbpA (B and E) and DbpB (C and F) as antigens. Each symbol represents the result of an GrazoprevirMedChemExpress Grazoprevir individual animal. Results are expressed as OD492 values and all samples were analysed in duplicate. The linePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,15 /DbpA and B Promote Arthritis and Post-Treatment Persistence in Miceindicates the mean of each group. Groups with same letter do not differ at 5 level of probability (Tukey’s HSD test). (TIF)AcknowledgmentsWe thank Fang-Ting Liang, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA for providing the B. burgdorferi strains used in the study, Seppo Neuvonen for help in statistical analyses, and Tiina Haarala, Tiina M il? Kirsi Sundholm-Heino and Anna Karvonen for excellent technical assistance. Centocor Research Development, Inc., Malvern, Pennsylvania, USA is acknowledged for providing anti-TNFalpha antibody.Author ContributionsConceived and designed the experiments: JS MKV JH. Performed the experiments: JS AJ MS JH. Analyzed the data: JS AJ MS JH. Contributed reagents/materials/analysis tools: JS MS MKV JH. Wrote the paper: JS AJ MS MKV JH.
With the identification of antibodies against N-methyl-D-aspartate receptors (NMDAR) a new subgroup of autoimmune encephalitis was described in 2007 [1]. The association of prominent psychiatric symptoms in the context of severe encephalitis and an underlying ovarian teratoma initially facilitated the discovery of this disorder [1, 2]. A majority of patients are female and the disease often occurs in childhood or early adolescence [3, 4]. In adul.Pment in mice although also B. burgdorferi strains that express DbpA or B alone, or the strain that is DbpA/B deficient, are able to colonize mouse joints. The progression of the joint manifestations in dbpAB/dbpAB infected mice is biphasic with peaks at 4 and 9?1 weeks of infection, and with histologically evident arthritis at 15 weeks of infection. The most important finding of the present study is the absence of post treatment borrelial DNA persistence in the joints of mice infected with DbpA/B deficient B. burgdorferi, while in the mice infected DbpA and B expressing B. burgdorferi, all joint samples were borrelial DNA positive up to 12 weeks after the treatment. One obvious explanation for this phenomenon is that DbpA and B assist the bacteria in invasion to decorin rich foci in mouse joints, which in turn allows evasion of antibiotic treatment and leads to post-treatment persistence of bacterial remnants in mouse joints. Based on the results of our anti-TNF-alpha immunosuppression experiments, the nature of the persisting material in the antibiotic treated mice appears to be non-cultivable bacterial remnants. The finding that only B. burgdorferi with a particular set of adhesins can form deposits of persisting remnants after treatment is thought provoking. We and others have shown that DbpA and B molecules of different B. burgdorferi sensu lato genospecies have different abilities to mediate binding to decorin and to decorin expressing cells [22, 26, 32]. Therefore, we will next focus on evaluating the contribution of DbpA and B of different B. burgdorferi sensu lato genospecies to dissemination of the infection, to arthritis development and to the post treatment persistence potential.Supporting InformationS1 Fig. IgG antibodies against C6, DbpA and DbpB in mouse serum samples. Antibody levels were measured using enzyme immunoassays with C6 peptide (A and D), DbpA (B and E) and DbpB (C and F) as antigens. Each symbol represents the result of an individual animal. Results are expressed as OD492 values and all samples were analysed in duplicate. The linePLOS ONE | DOI:10.1371/journal.pone.0121512 March 27,15 /DbpA and B Promote Arthritis and Post-Treatment Persistence in Miceindicates the mean of each group. Groups with same letter do not differ at 5 level of probability (Tukey’s HSD test). (TIF)AcknowledgmentsWe thank Fang-Ting Liang, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA for providing the B. burgdorferi strains used in the study, Seppo Neuvonen for help in statistical analyses, and Tiina Haarala, Tiina M il? Kirsi Sundholm-Heino and Anna Karvonen for excellent technical assistance. Centocor Research Development, Inc., Malvern, Pennsylvania, USA is acknowledged for providing anti-TNFalpha antibody.Author ContributionsConceived and designed the experiments: JS MKV JH. Performed the experiments: JS AJ MS JH. Analyzed the data: JS AJ MS JH. Contributed reagents/materials/analysis tools: JS MS MKV JH. Wrote the paper: JS AJ MS MKV JH.
With the identification of antibodies against N-methyl-D-aspartate receptors (NMDAR) a new subgroup of autoimmune encephalitis was described in 2007 [1]. The association of prominent psychiatric symptoms in the context of severe encephalitis and an underlying ovarian teratoma initially facilitated the discovery of this disorder [1, 2]. A majority of patients are female and the disease often occurs in childhood or early adolescence [3, 4]. In adul.