Remodeling and Restraining Lung Tissue Damage Through the Regulation of Respiratory Immune Responses

Tissue damage caused by various stimuli under certain conditions, such as biological and environmental cues, can actively induce systemic and/or local immune responses. Therefore, understanding the immunological perspective would be critical to not only regulating homeostasis of organs and tissues but also to restrict and remodel their damage.Lungs serve as one of the key immunological organs, and thus, in the present article, we focus on the innate and adaptive immune systems involved in remodeling and engineering lung tissue. Innate immune cells are known to react immediately to damage. Macrophages, one of the most widely studied types of innate immune cells, are known to be involved in tissue damage and remodeling, while type 2 innate lymphoid cells (ILC2s) have recently been revealed as an important cell type responsible for tissue remodeling. On the other hand, adaptive immune cells are also involved in damage control. In particular, resident memory T cells in the lung prevent prolonged disease that causes tissue damage. In this review, we first outlined the structure of the respiratory system with biological and environmental cues and the innate/adaptive immune responses in the lung. It is our hope that understanding an immunological perspective for tissue remodeling and damage control in the lung will be beneficial for stakeholders in this area.

Enhancement of Immune Responses Elicited by Nanovaccines through a Cross-Presentation Pathway

Numerous studies have aimed to develop novel advanced vaccines, in part because traditional vaccines have been unsuccessful in preventing rapidly emerging and reemerging viral and bacterial infections. There is a need for an advanced vaccine delivery system to ensure the successful induction of humoral and cellular immune responses. In particular, the ability of nanovaccines to modulate intracellular antigen delivery by inducing exogenous antigens (loaded onto major histocompatibility complex class 1 molecules) in CD8+ T cells, the so-called cross-presentation pathway, has attracted a great deal of attention. Protection against viral and intracellular bacterial infections relies on cross-presentation.This review discusses the advantages, requirements, and preparation of nanovaccines, the cross-presentation mechanism, the several parameters affecting cross-presentation by nanovaccines, and future perspectives.

Intranasal Vaccination with OuterMembrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus

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.

Mucosal Vaccine Delivery Using Mucoadhesive Polymer Particulate Systems

Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been interested in many researchers because mucosal immune responses play part in the first line of defense against pathogens. However, mucosal vaccination should find out an efficient antigen delivery system because the antigen should be protected from degradation and clearance, it should be targeted to mucosal sites, and it should stimulate mucosal and systemic immunity. Accordingly, mucoadhesive polymeric particles among the polymeric particles have gained much attention because they can protect the antigen from degradation, prolong the residence time of the antigen at the target site, and control the release of the loaded vaccine, and results in induction of mucosal and systemic immune responses. In this review, we discuss advances in the development of several kinds of mucoadhesive polymeric particles for mucosal vaccine delivery.

Mucosal Vaccine Delivery Using Mucoadhesive Polymer Particulate Systems

Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been interested in many researchers because mucosal immune responses play part in the first line of defense against pathogens. However, mucosal vaccination should find out an efficient antigen delivery system because the antigen should be protected from degradation and clearance, it should be targeted to mucosal sites, and it should stimulate mucosal and systemic immunity. Accordingly, mucoadhesive polymeric particles among the polymeric particles have gained much attention because they can protect the antigen from degradation, prolong the residence time of the antigen at the target site, and control the release of the loaded vaccine, and results in induction of mucosal and systemic immune responses. In this review, we discuss advances in the development of several kinds of mucoadhesive polymeric particles for mucosal vaccine delivery.

Short-chain Fatty Acids Inhibit Staphylococcal Lipoprotein-induced Nitric Oxide Production in Murine Macrophages

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.

T Cell Receptor Signaling That Regulates the Development of Intrathymic Natural Regulatory T Cells

T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.

The stress of weaning influences serum levels of acute-phase proteins, iron-binding proteins, inflammatory cytokines, cortisol, and leukocyte subsets in Holstein calves

The purpose of our study was to investigate changes in immunological parameters induced by weaning stress (including milk restriction) in calves. Fifteen Holstein calves were subjected to weaning at 6 weeks of age. Blood samples were collected at -14, -7, -2, 1, 3, and 5 days post-weaning (DPW; 0 DPW = 42 days). Weaning caused significant (p < 0.01) increases in the neutrophil (NE):lymphocyte (LY) ratio at 5 DPW with a significant (p < 0.05) reduction of LYs. The concentration of acute-phase proteins (haptoglobin and serum amyloid A) also increased significantly (p < 0.05) at 3 and 5 DPW compared to -2 DPW. Levels of the iron-binding protein lactoferrin decreased significantly (p < 0.05) after weaning. Serum tumor necrosis factor-alpha and cortisol levels were elevated (p < 0.05) at 3 DPW, while those of serum interferon-gamma decreased (p < 0.05) at 1 and 3 DPW compared to levels observed before weaning. Weaning significantly (p < 0.05) decreased the percentage of CD25+ T cells in the peripheral blood. In conclusion, weaning stress affected the NE:LY ratio along with the levels of acute phase proteins, lactoferrin, cortisol, and inflammatory cytokines in the peripheral blood of calves. Weaning stress may induce an acute phase response possibly through the elevation of cortisol production and modulation of inflammatory cytokines.

Identification of a kidney-specific mouse organic cation transporter like-1 (mOCTL1)

Organic ion transporters are expressed in various tissues that transport endogenous and exogenous compounds including their metabolites. There are organic anion transporter (OAT), organic cation transporter (OCT), organic anion transporter like protein (OATLP) and organic cation transporter like (OCTL). Considering the variety of charged organic ionic compounds, the existence of numerous isoforms of organic ion transporters can be assumed. In the present study, we have searched for a new isoform in the expressed sequence tag (EST) database using human organic anion transporter 4 (hOAT4) amino acid sequence as a "query". We found a candidate clone (BC021449) from the mouse kidney cDNA library. This clone was identified as an ortholog of ORCTL3 or OCTL-1. The mOCTL1 cDNA consists of 2016 base pairs encoding 551 amino acid residues with 12 putative transmembrane domains. The deduced amino acid sequence of mOCTL1 showed 35 to 40% identity to those of the other members of the OATs and OCTs. According to the tissue distribution, examined by Northern blot analysis, about a 2.4-kb transcript of mOCTL1 was observed in the kidney. About a 90-kDa band was detected when Western blot analysis in the mouse kidney was done by using antibody against synthesized oligopeptide of mOCTL1. The immunohistochemical result showed that mOCTL1 was stained at the glomerulus (the parietal epithelial cells and podocytes), pars recta of proximal tubule, distal convoluted tubules, connecting tubules and collecting tubules. From these results, we conclude that mOCTL1 may be a candidate for an organic ion transporter isoform in the mouse kidney.