Search

Cholera remains a major global public health problem, for which oral cholera vaccines (OCVs) being a valuable strategy. Patients, who have recovered from cholera, develop antibody responses against LPS, cholera toxin (CT), toxin-coregulated pilus (TCP) major subunit A (TcpA) and other antigens; thus, these responses are potentially important contributors to immunity against

The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8+T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+cells. CD5hiLy6C+cells differ from CD5loLy6C–and CD5hiLy6C–cells in terms of gene expression profiles and functional properties. Moreover, CD5hiLy6C+cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5hiLy6C+cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8+T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8+T cells by co-opting tonic type I interferon signaling.

Bacteriophages, simply phages, have long been used as a potential alternative to antibiotics for livestock due to their ability to specifically kill enterotoxigenic Escherichia coli (ETEC), which is a major cause of diarrhea in piglets. However, the control of ETEC infection by phages within intestinal epithelial cells, and their relationship with host immune responses, remain poorly understood. In this study, we evaluated the effect of phage EK99P-1 against ETEC K99-infected porcine intestinal epithelial cell line (IPEC-J2). Phage EK99P-1 prevented ETEC K99-induced barrier disruption by attenuating the increased permeability mediated by the loss of tight junction proteins such as zonula occludens-1 (ZO-1), occludin, and claudin-3. ETEC K99-induced inflammatory responses, such as interleukin (IL)-8 secretion, were decreased by treatment with phage EK99P-1. We used a IPEC-J2/peripheral blood mononuclear cell (PBMC) transwell co-culture system to investigate whether the modulation of barrier disruption and chemokine secretion by phage EK99P-1 in ETEC K99-infected IPEC-J2 would influence immune cells at the site of basolateral. The results showed that phage EK99P-1 reduced the mRNA expression of ETEC K99-induced pro-inflammatory cytokines, IL-1β and IL-8, from PBMC collected on the basolateral side. Together, these results suggest that phage EK99P-1 prevented ETEC K99-induced barrier dysfunction in IPEC-J2 and alleviated inflammation caused by ETEC K99 infection. Reinforcement of the intestinal barrier, such as regulation of permeability and cytokines, by phage EK99P-1 also modulates the immune cell inflammatory response.

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against

STAT1 serves as a gatekeeper for naïve CD8 + T cell homeostasis by restraining type I IFN-STAT4-mTOR signaling axis.

We investigated the relationship between family conflict resolution and depression, focusing on each component of family conflict resolution to determine which factors have stronger associations with depression. We used data from 2008 to 2015 of the Korea Welfare Panel Study. Our final sample included 3565 participants. For each participant, we included at least 2-8 years of follow-up data with a mean follow-up time of 4.05 ± 2.52 years. To identify the relationship between new-onset depressive symptoms and participants' family conflict resolution styles, we performed generalized estimating equation analysis with autoregressive working correlations to estimate adjusted odds ratios for new-onset depressive symptoms adjusted for covariates. Compared with positive family conflict resolution, negative family conflict resolution had a higher odds ratio for depressive symptoms (aOR 1.80, 95% CI 1.42-2.29). This relationship was strongly founded on participants who were women (aOR 2.35, 95% CI 1.55-3.94) with experience of verbal aggression (aOR 1.84, 95% CI 1.42-2.37) and threatening behaviors (aOR 1.89, 95% CI 1.25-2.85). Negative family conflict resolution has long-term associations with an elevated risk of depressive symptoms. In particular, we observed higher risks of depression with verbal and psychological conflict than with physical conflict. Health care providers and health policymakers should support the management and development of methods for dealing with family conflict to improve mental health at a family level, as well as an individual level.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Gastrointestinal tract is the first organ to be directly affected upon fasting. However, little is known about how the fasting influences intestinal immune system. In the present study, we focused on the changes of intestinal dendritic cells (DCs) in mice upon short-term fasting and how the changes influence protective immunity against Listeria monocytogenes (LM) infection. We found that the fasting induces an increased number of CD103+CD11b- DCs in both small intestinal lamina propria (SI LP) and mesenteric lymph nodes (mLN) and the SI LP CD103+CD11b- DCs undergo an active proliferation and migration by increased levels of GM-CSF and CCR7, respectively. At 24 hours post-infection (hpi) of LM, there was a significant reduction of bacterial burden from the spleen, liver, and mLN of the short-term fasting mice compared to those of ad libitum mice. Accordingly, short-term fasting mice showed enhanced survival against LM infection when compared with ad libitum mice. Furthermore, significantly high amount of TGF-β2 and Aldh1a2 expression from CD103+CD11b- DCs in mouse infected with LM sequentially caused the following events: the increase of Foxp3+ Tregs, preferential change in the composition of CD103+ to CD103- DCs, and the induction of IFN-γ producing cells. Collectively, increase of intestinal CD103+ DCs by short-term fasting is a key player for protection against LM infection through the changes of functional features from tolerogenic to Th1 immunogenic.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with

Intergenerational transmission, which refers to the similarity between parent and their children, is a possible explanation of adolescent physical activity (PA). However, only a few existing studies explore the relationship of parent-adolescent PA in East Asian countries. Therefore, this study aimed to investigate the association of parent-adolescent PA using a nationally representative data in Korea with a large sample size.Data were collected from the Korean National Health and Nutrition Examination Survey conducted from 2010 to 2014. The authors performed a linear mixed effects regression analysis with 1342 cases after using log conversion of parent and adolescent moderate- to vigorous-intensity physical activity (MVPA) levels.In the study, the median MVPA of adolescents was 150 (interquartile range: 360) minutes per week. Adolescent MVPA levels were significantly correlated with their mother's MVPA (β = 0.055, P = .02). Similar findings of greater association in girls and younger adolescents (age: 13-15 y) were found in subgroup analysis (girls: β = 0.073, P = .05; younger adolescents: β = 0.103, P = .001).Increasing maternal PA levels could stimulate their adolescent's PA levels. Therefore, intervention at the family level may lead to an increase in adolescent PA levels.

Cytokine induction is often critical for the host defense during acute immune responses while, if not tightly regulated, it may cause an immunological pathology coincident with tissue damage. Despite the fact that gram-positive bacterial infection has become increasingly prevalent, immune modulation induced by lipoteichoic acid (LTA), the major cell wall component of gram-positive bacteria has not been studied thoroughly at the cellular level. In the current study, tolerance induction in mouse bone marrow-derived dendritic cells (BMDCs) treated with single or repeated stimulation of Staphylococcus aureus LTA was compared with those of Escherichia coli lipopolysaccharide (LPS). The results showed that repeated LTA stimulation significantly suppressed pro-inflammatory cytokine (TNF-α and IL-6) production in BMDCs, comparable to that of LPS, but with less extent, down-regulated IL-10 and enhanced the inhibitory molecule, LAG-3-associated protein (LAP). Furthermore, we observed a sustained expression of unique negative regulators, Toll interacting protein (TOLLIP) and Indoleamine 2,3-dioxygenase (IDO), in BMDCs treated with LTA. A transient hyporesponsiveness period appeared when DCs were treated repeatedly with LTA or LPS showing a distinctive pattern. Intriguingly, LPS exposure induced cross tolerance to LTA while LTA exposure did not to LPS, implicating that a distinct signaling components are involved in response to LTA. Collectively, a distinct immune regulation appeared to be responsible for the LPS- and LTA-induced tolerance on cytokine production, expression of surface markers and intracellular proteins.

Background Despite the positive effect of community-based mental health centers, the utilization of professional mental health services appears to be low. Therefore, we analyzed the relationship between regional recognition of mental health centers and utilization of professional mental health services. Methods We used data from the Community Health Survey (2014) and e-provincial indicators. Only those living in Seoul, who responded that they were either feeling a lot of stress or depression, were included in the study. Multiple logistic regression analysis using generalized estimating equations was performed to examine both individual- and regional-level variables associated with utilization of professional mental health services. Results Among the 7338 participants who reported depression or stress, 646 (8.8%) had consulted a mental health professional for their symptoms. A higher recognition rate of mental health centers was associated with more utilization of professional mental health services (odds ratio [OR]=1.05, 95% confidence interval [CI]=1.03–1.07). Conclusions Accessibility to professional mental health services could be improved depending on the general population's recognition and attitudes toward mental health centers. Therefore, health policy-makers need to plan appropriate strategies for changing the perception of mental health services and informing the public about both the benefits and functions of mental health centers.

Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naive T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8+T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8+ T cells than naive cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8+ T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens. Naive T cells establish self-tolerance via negative selection of cells with strong reactivity for self-peptide/MHC complexes, but undergo T-cell receptor (TCR) desensitisation when leaving the thymus. Here, Choet al.show that TCR desensitisation correlates with cell-surface density of the phosphatase CD45.

This study aims to determine whether changes in sleep quantity and quality in childhood are associated with incidence of depressive symptoms. We used the three waves of the Korean Children & Youth Panel Survey (2011–2013). Statistical analysis using a generalized estimating equation model was performed. The 2,605 subjects analyzed included 1,453 students in 2012 and 1,152 students in 2013 without depressive symptoms in the prior year. We found that deteriorated or consistently poor sleep quality were important risk factors for depressive symptoms in children. We suggest that early detection and intervention of poor sleep quality in elementary school is required to reduce early onset depressive symptoms.

Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. STATE OF SIGNIFICANCE: In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection.