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Current Topics in Microbiology and Immunology

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https://www.readbyqxmd.com/read/28929194/adapting-secretory-proteostasis-and-function-through-the-unfolded-protein-response
#1
Madeline Y Wong, Andrew S DiChiara, Patreece H Suen, Kenny Chen, Ngoc-Duc Doan, Matthew D Shoulders
Cells address challenges to protein folding in the secretory pathway by engaging endoplasmic reticulum (ER)-localized protective mechanisms that are collectively termed the unfolded protein response (UPR). By the action of the transmembrane signal transducers IRE1, PERK, and ATF6, the UPR induces networks of genes whose products alleviate the burden of protein misfolding. The UPR also plays instructive roles in cell differentiation and development, aids in the response to pathogens, and coordinates the output of professional secretory cells...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28929193/immune-regulation-by-ubiquitin-tagging-as-checkpoint-code
#2
Peng Zeng, Jieyu Ma, Runqing Yang, Yun-Cai Liu
The immune system is equipped with effective machinery to mobilize its activation to defend invading microorganisms, and at the same time, to refrain from attacking its own tissues to maintain immune tolerance. The balance of activation and tolerance is tightly controlled by diverse mechanisms, since breakdown of tolerance could result in disastrous consequences such as the development of autoimmune diseases. One of the mechanisms is by the means of protein ubiquitination, which involves the process of tagging a small peptide ubiquitin to protein substrates...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#3
Kenji Chamoto, Muna Al-Habsi, Tasuku Honjo
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#4
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28929190/mining-the-complex-family-of-protein-tyrosine-phosphatases-for-checkpoint-regulators-in-immunity
#5
Claudia Penafuerte, Luis Alberto Perez-Quintero, Valerie Vinette, Teri Hatzihristidis, Michel L Tremblay
The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-tolerance, and have gained recognition as true immune system checkpoint modulators...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28918539/accelerating-vaccine-development-during-the-2013-2016-west-african-ebola-virus-disease-outbreak
#6
Elizabeth S Higgs, Sheri A Dubey, Beth A G Coller, Jakub K Simon, Laura Bollinger, Robert A Sorenson, Barthalomew Wilson, Martha C Nason, Lisa E Hensley
The Ebola virus disease outbreak that began in Western Africa in December 2013 was unprecedented in both scope and spread, and the global response was slower and less coherent than was optimal given the scale and pace of the epidemic. Past experience with limited localized outbreaks, lack of licensed medical countermeasures, reluctance by first responders to direct scarce resources to clinical research, community resistance to outside interventions, and lack of local infrastructure were among the factors delaying clinical research during the outbreak...
September 17, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28918538/genetic-manipulation-of-borrelia-spp
#7
Dan Drecktrah, D Scott Samuels
The spirochetes Borrelia (Borreliella) burgdorferi and Borrelia hermsii, the etiologic agents of Lyme disease and relapsing fever, respectively, cycle in nature between an arthropod vector and a vertebrate host. They have extraordinarily unusual genomes that are highly segmented and predominantly linear. The genetic analyses of Lyme disease spirochetes have become increasingly more sophisticated, while the age of genetic investigation in the relapsing fever spirochetes is just dawning. Molecular tools available for B...
September 17, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28918537/reverse-genetics-of-filoviruses
#8
Thomas Hoenen, Janine Brandt, Yíngyún Caì, Jens H Kuhn, Courtney Finch
Reverse genetics systems are used for the generation of recombinant viruses. For filoviruses, this technology has been available for more than 15 years and has been used to investigate questions regarding the molecular biology, pathogenicity, and host adaptation determinants of these viruses. Further, reporter-expressing, recombinant viruses are increasingly used as tools for screening for and characterization of candidate medical countermeasures. Thus, reverse genetics systems represent powerful research tools...
September 17, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900683/microrna-in-immune-regulation
#9
Cheng-Jang Wu, Li-Fan Lu
The immune system protects us from enormously diverse microbial pathogens but needs to be tightly regulated to avoid deleterious immune-mediated inflammation and tissue damage. A wide range of molecular determinants and cellular components work in concert to control the magnitude and duration of a given immune response. In the past decade, microRNAs (miRNAs), a major class of small non-coding RNA species, have been extensively studied as key molecular players in immune regulation. In this chapter, we will discuss how miRNAs function as negative regulators to restrict innate and adaptive immune responses...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900682/treatment-of-staphylococcus-aureus-infections
#10
Michael Z David, Robert S Daum
Staphylococcus aureus, although generally identified as a commensal, is also a common cause of human bacterial infections, including of the skin and other soft tissues, bones, bloodstream, and respiratory tract. The history of S. aureus treatment is marked by the development of resistance to each new class of antistaphylococcal antimicrobial drugs, including the penicillins, sulfonamides, tetracyclines, glycopeptides, and others, complicating therapy. S. aureus isolates identified in the 1960s were sometimes resistant to methicillin, a ß-lactam antimicrobial active initially against a majority S...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900681/regulatory-dendritic-cells
#11
Katsuaki Sato, Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi
Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900680/coordinating-organismal-metabolism-during-protein-misfolding-in-the-er-through-the-unfolded-protein-response
#12
Vishwanatha K Chandrahas, Jaeseok Han, Randal J Kaufman
The endoplasmic reticulum (ER) is a cellular organelle responsible for folding of secretory and membrane proteins. Perturbance in ER homeostasis caused by various intrinsic/extrinsic stimuli challenges the protein-folding capacity of the ER, leading to an ER dysfunction, called ER stress. Cells have developed a defensive response to adapt and/or survive in the face of ER stress that may be detrimental to cell function and survival. When exposed to ER stress, the cell activates a complex and elaborate signaling network that includes translational modulation and transcriptional induction of genes...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#13
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#14
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900677/tim-3-lag-3-and-tigit
#15
Nicole Joller, Vijay K Kuchroo
Co-inhibitory receptors play a key role in regulating T cell responses and maintaining immune homeostasis. Their inhibitory function prevents autoimmune responses but also restricts the ability of T cells to mount effective immune responses against tumors or persistent pathogens. T cells express a module of co-inhibitory receptors, which display great diversity in expression, structure, and function. Here, we focus on the co-inhibitory receptors Tim-3, Lag-3, and TIGIT and how they regulate T cell function, maintenance of self-tolerance, their role in regulating ongoing T cell responses at peripheral tissues, and their synergistic effects in regulating autoimmunity and antitumor responses...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28884191/the-appearance-and-diversification-of-receptors-for-igm-during-vertebrate-evolution
#16
Srinivas Akula, Lars Hellman
Three different receptors that interact with the constant domains of IgM have been identified: the polymeric immunoglobulin (Ig) receptor (PIGR), the dual receptor for IgA/IgM (FcαµR) and the IgM receptor (FcµR). All of them are related in structure and located in the same chromosomal region in mammals. The functions of the PIGRs are to transport IgM and IgA into the intestinal lumen and to saliva and tears, whereas the FcαµRs enhance uptake of immune complexes and antibody coated bacteria and viruses by B220+ B cells and phagocytes, as well as dampening the Ig response to thymus-independent antigens...
September 8, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28879525/colonic-spirochetes-what-has-genomics-taught-us
#17
David John Hampson, Penghao Wang
The 'colonic' spirochetes assigned to the genus Brachyspira are slow-growing anaerobic bacteria. The genus includes both pathogenic and non-pathogenic species, and these variously colonise the large intestines of different species of birds and animals, including humans. Scientific understanding of the physiology and molecular biology of Brachyspira spp. remains very limited compared with that of other pathogenic spirochetes, and there are few descriptions of successful genetic manipulations undertaken to investigate gene function...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28879524/uptake-of-clostridial-neurotoxins-into-cells-and-dissemination
#18
Chloé Connan, Michel R Popoff
Clostridial neurotoxins, botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT), are potent toxins, which are responsible for severe neurological diseases in man and animals. BoNTs induce a flaccid paralysis (botulism) by inhibiting acetylcholine release at the neuromuscular junctions, whereas TeNT causes a spastic paralysis (tetanus) by blocking the neurotransmitter release (glycine, GABA) in inhibitory interneurons within the central nervous system. Clostridial neurotoxins recognize specific receptor(s) on the target neuronal cells and enter via a receptor-mediated endocytosis...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28879523/regulatory-t-cells-molecular-and-cellular-basis-for-immunoregulation
#19
Yosuke Togashi, Hiroyoshi Nishikawa
CD4(+) regulatory T cells (Tregs) are a highly immune-suppressive subset of CD4(+) T cells, characterized by expression of the master regulatory transcription factor FOXP3. Tregs are proven to play central roles in the maintenance of self-tolerance in healthy individuals. Tregs are involved in maintaining immune homeostasis: they protect hosts from developing autoimmune diseases and allergy, whereas in malignancies, they promote tumor progression by suppressing anti-tumor immunity. Elucidating factors influencing Treg homeostasis and function have important implications for understanding disease pathogenesis and identifying therapeutic opportunities...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28879522/cell-non-autonomous-upr-er-signaling
#20
Soudabeh Imanikia, Ming Sheng, Rebecca C Taylor
The UPR(ER) is an important regulator of secretory pathway homeostasis, and plays roles in many physiological processes. Its broad range of targets and ability to modulate secretion and membrane trafficking make it perfectly positioned to influence intercellular communication, enabling the UPR(ER) to coordinate physiological processes between cells and tissues. Recent evidence suggests that the activation of the UPR(ER) can itself be communicated between cells. This cell non-autonomous route to UPR(ER) activation occurs in multiple species, and enables organism-wide responses to stress that involve processes as diverse as immunity, metabolism, aging and reproduction...
September 7, 2017: Current Topics in Microbiology and Immunology
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