TFH-IgA Responses Keep Microbiota in Check

In this issue of Cell Host & Microbe, Kubinak et al. (2015) demonstrate that gut microbiota-mediated signaling through MyD88 in CD4+ T cells induces their differentiation into T follicular helper (TFH) cells that promote affinity-matured microbiota antigen-specific immunoglobulin A (IgA) responses. These TFH-driven IgA responses are essential for maintaining gut bacterial diversity and a healthy microbiota

Porphyromonas gingivalis Sinks Teeth into the Oral Microbiota and Periodontal Disease

Periodontitis is linked to polymicrobial interactions and the presence of Porphyromonas gingivalis. In this issue of Cell Host & Microbe, Hajishengallis et al. (2011) demonstrate that P. gingivalis colonization in the oral cavity changes the composition of the oral commensal microbiota and accelerates microbiota-mediated bone-destructive periodontitis, indicating that this single, low-abundance species is a keystone in periodontal disease

Clarithromycin expands CD11b+Gr-1+ MDSC-like cells

Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides

Non-HDL-C and CVD

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes. Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group. Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19–5.72), 2.02 (0.95–4.29), 2.10 (1.01–4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction. Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers

15. ゼミノームの放射線治療成績(第5回佐藤外科例会,第488回千葉医学会例会)

Performance of the MDSINE inference algorithms on simulated data with different sequencing depths. Simulations assumed an underlying dynamical systems model with ten species observed over 30 days with 27 time points sampled and an invading species at day 10. Performance of the four MDSINE inference algorithms, maximum likelihood ridge regression (MLRR), maximum likelihood constrained ridge regression (MLCRR), Bayesian adaptive lasso (BAL), and Bayesian variable selection (BVS), were compared. Algorithm performance was assessed using four different metrics: (a) root mean-square error (RMSE) for microbial growth rates; (b) RMSE for microbial interaction parameters; (c) RMSE for prediction of microbe trajectories on held-out subjects given only initial microbe concentrations for the held-out subject; and (d) area under the receiver operator curve (AUC ROC) for the underlying microbial interaction network. Lower RMSE values indicate superior performance, whereas higher AUC ROC values indicate superior performance. (PDF 182 kb

MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses

Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE’s utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-0980-6) contains supplementary material, which is available to authorized users

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies

Association between social support and place of delivery: a cross-sectional study in Kericho, Western Kenya

Background: An estimated 358,000 maternal deaths still occur worldwide each year. The place of delivery is of great significance to the reduction of maternal mortality. Moreover, socio-economic factors, cultural traits, and local customs are associated with health-seeking behavior. This study aimed to explore determinants of association between social support and place of delivery. Methods: This cross-sectional study was conducted from September to November 2011 at Sosiot Health Center, Kericho West District, Kenya. Participants were 303 mothers who brought their babies to the health center for immunization within their first year of life. Women underwent a structured interview using a questionnaire on demographic characteristics and their experiences of delivery including place of delivery and social support. Results: The proportion of deliveries at health facilities was significantly higher in unmarried than married women (93% and 78%, respectively; P = 0.008). Unmarried women whose mothers supported them in housework and whose sisters helped them fetch water were more likely to deliver at health facilities (P = 0.002 and 0.042, respectively) than those without this support. However, married women whose husbands supported them in farming and whose neighbors helped them fetch water were less likely to deliver at health facilities (P = 0.003 and 0.021, respectively) than those without this support. Married women who were advised to deliver at a health facility by their mother-in-law or health staff were more likely to deliver at health facilities (P = 0.015 and 0.022, respectively) than those who did not receive this advice. Multivariate analysis revealed that married women were more likely to deliver at health facilities if they were highly educated (odds ratio [OR] = 2.5); had financial capability (OR = 4.3); had medical insurance (OR = 4.2); were primiparous (OR = 3.5); did not have the support of sisters-in-law for fetching water (OR = 2.2); or were advised to deliver at a health facility by family or neighbors (OR = 2.5).Conclusions: Promotion of delivery at health facilities requires approaches that consider women\u27s social situation, since factors influencing place of delivery differ for married and unmarried women