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In sepsis, the pathology involves a shift from a proinflammatory state toward an immunosuppressive phase. We previously showed that an agonistic anti‐TLR4 antibody induced long‐term endotoxin tolerance and suppressed antigen‐specific secondary IgG production when primed prior to immunization with antigen. These findings led us to speculate that TLR4‐induced innate tolerance due to primary infection causes an immunosuppressive pathology in sepsis. Therefore, the mechanism underlying impaired antigen‐specific humoral immunity by the TLR4 antibody was investigated. We showed, in a mouse model, that primary antigen‐specific IgG responses were impaired in TLR4 antibody‐induced tolerized mice, which was the result of reduced numbers of antigen‐specific GC B cells and plasma cells. Ovalbumin‐specific CD4 and CD8 T‐cell responses were impaired in TLR4 antibody‐injected OT‐I and ‐II transgenic mice ex vivo. Adoptive transfer studies demonstrated suppression of OVA‐specific CD4 and CD8 T‐cell responses by the TLR4 antibody in vivo. The TLR4 antibody induced Gr1+CD11b+ myeloid‐derived suppressor cell (MDSC) expansion with suppression of T‐cell activation. Monocytic MDSCs were more suppressive and exhibited higher expression of PD‐L1 and inducible nitric oxidase compared with granulocytic MDSCs. In conclusion, immune tolerance conferred by TLR4 activation induces the expansion of monocytic MDSCs, which impairs antigen‐specific T‐cell priming and IgG production. Sepsis pathology is shifted from an acute proinflammatory phase toward a delayed immunosuppressive phase, and the immunosuppressive pathology is not well‐understood. Here, we demonstrate that immune tolerance conferred by TLR 4 activation induces the expansion of monocytic myeloid‐derived suppressor cells, which impairs antigen‐specific T‐cell priming and IgG production. [ABSTRACT FROM AUTHOR]

Aim: The use of problem lists is encouraged to overcome the inconsistency in reporting comprehensive geriatric assessment results. The present study aimed to identify the latent variables influencing the use of geriatrician problem lists. Methods: Surveys were sent to all geriatricians registered with the Japan Geriatrics Society (n = 1439) as of November 2015, and responses (n = 204) were analyzed with univariate and exploratory factor analyses. To account for active, inactive and tentative items, the survey addressed "disease," "symptom" and "condition" separately. Results: Most geriatricians (34.8%) composed problem lists for interdisciplinary information sharing. Nearly half of the respondents (46.6%) created problem lists for every patient. Information omissions were mainly due to the exclusion of information from other specialties (26% for omitted diseases and 12.3% for omitted symptoms), lack of time (25.5% for omitted diseases, 22.1% for omitted symptoms and 26.5% for omitted conditions), and lack of standardization of terminologies regarding observed diseases, symptoms and conditions (12.3% for omitted diseases, 19.6% for omitted symptoms and 16.7% for omitted conditions). An exploratory factor analysis, based on 20 predefined symptoms and conditions that are frequently omitted from problem lists, showed that considering the symptom "geriatric syndromes" and the condition "assistance needs in medication management" are crucial for improving problem list comprehensiveness. Conclusions: Geriatricians commonly use problem lists; however, there is considerable variation regarding the problems listed and their relationships. The listings of "geriatric syndrome" and "assistance needs in medication management" are crucial for improving problem list comprehensiveness. Geriatr Gerontol Int 2019; 19: 159–164. [ABSTRACT FROM AUTHOR]

A total of 23 strains of bifidobacteria taxonomically belonging to five species were tested for their potent immunomodulatory effect using a combination of two methods: the NF-κB-reporter assay using a toll-like receptor 2-expressing transfectant (HEKpTLR2 system) and the mitogenic assay using porcine Peyer's patches immunocompetent cells. Among the four preselected strains from different immunomodulatory groups, Bifidobacterium breve MCC-117 was able to efficiently modulate the inflammatory response triggered by enterotoxigenic Escherichia coli (ETEC) in a porcine intestinal epithelial (PIE) cell line. Moreover, using PIE cells and swine Peyer's patches immunocompetent cell co-culture system, we demonstrated that the immunoregulatory effect of B. breve MCC-117 was related to the capacity of the strain to influence PIE and immune cell interactions, leading to the stimulation of regulatory T cells. The results suggested that bifidobacteria that express high activity in both the HEKpTLR2 and the mitogenic assays may behave like potential anti-inflammatory strains. The combination of the HEKpTLR2 system, the evaluation of mitogenic activity and PIE cells will be of value for the development of new immunologically functional foods and feeds that could prevent inflammatory intestinal disorders. Although our findings should be proven in appropriate experiments in vivo, the results of the present work provide a scientific rationale for the use of B. breve MCC-117 to prevent ETEC-induced intestinal inflammation. [ABSTRACT FROM AUTHOR]

Interleukin-17 (IL-17) is a CD4 T cell cytokine. In this report, we investigated the effects of this cytokine on the elaboration of proangiogenic factors by lung fibroblasts. After stimulation with a wide range of doses of IL-17, fibroblasts produced more amount of various kinds of angiogenic factors including NO, HGF, MCP-1, KC, MIP-2, PGE1, PGE2 and VEGF in a dose-dependent manner. Treatment with a COX-1 and COX-2 inhibitor indomethacin did not impair IL-17-induced HGF and VEGF secretion in fibroblasts. In addition, TNF-α alone stimulated the elaboration of KC, MIP-2, PGE2 and VEGF in fibroblasts. IL-17 and TNF-α in combination up-regulated elaboration of these proangiogenic factors additively or synergistically. Moreover, conditioned media (CM) from IL-17-stimulated fibroblasts showed significantly higher activity on endothelial cell growth than those from non-treated control cells. These results indicate that IL-17 up-regulates elaboration of various proangiogenic factors, and modulates macrophage-derived TNF-α-induced production of KC, MIP-2, PGE2 and VEGF by fibroblasts. Our findings also demonstrate that IL-17 might be a potential contributor to the inflammatory angiogenesis via induction of proangiogenic factors by stromal fibroblasts. [Copyright &y& Elsevier]

The article focuses on the case of a 29 year old woman who presented to physicians with severe dyspnoea and a history of recurrent respiratory infections. A discussion of her initial treatment for asthma with oxygen, nebulized salibutamol and dexamethasone is presented. A CT scan of her chest which revealed a narrowing of her entire trachea and and an anomalous origin of the right upper lobe bronchus with a narrow opening is discussed. Her final diagnosis of congenital tracheal stenosis with viral respiratory infection, and her treatment and recovery is examined.

Abstract: Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that are present in most invertebrates and vertebrates. Mammals have four PGRPs, PGLYRP1–4. In the present study, we cloned the cDNAs encoding porcine PGLYRP3 and 4 from the esophagus of adult swine. The length of the complete open reading frames of porcine PGLYRP3 and 4 are identical and contain 1125bp encoding 374 amino acid residues. The amino acid sequences of these two proteins were more similar to their human orthologs (78.9% [PGLYRP3] and 73.9% [PGLYRP4]) than to their mouse orthologs (71.3% [PGLYRP3] and 67.9% [PGLYRP4]). Expression analysis revealed that both PGLYRP3 and 4 were more strongly expressed in digestive tract, especially the esophagus, than in immune organs such as spleen or mesenteric lymph nodes in both newborn and adult swine. To analyze the subcellular distribution of porcine PGLYRP1–4, we constructed transfectant cell lines. Western blot and flow cytometric analyses revealed that porcine PGLYRP3 and 4 are not only secreted, but also expressed on the cell surface, unlike PGLYRP1 and 2. These results should help contribute to the understanding of PGLYRP3- and 4-mediated immune responses via their recognition of intestinal microorganisms in newborn and adult swine. [Copyright &y& Elsevier]