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Bacterial adaptive immunity

Zubair Ahmed Ratan, Young-Jin Son, Mohammad Faisal Haidere, Bhuiyan Mohammad Mahtab Uddin, Md Abdullah Yusuf, Sojib Bin Zaman, Jong-Hoon Kim, Laila Anjuman Banu, Jae Youl Cho
Bacteria and archaea possess adaptive immunity against foreign genetic materials through clustered regularly interspaced short palindromic repeat (CRISPR) systems. The discovery of this intriguing bacterial system heralded a revolutionary change in the field of medical science. The CRISPR and CRISPR-associated protein 9 (Cas9) based molecular mechanism has been applied to genome editing. This CRISPR-Cas9 technique is now able to mediate precise genetic corrections or disruptions in in vitro and in vivo environments...
2018: Therapeutic Advances in Medical Oncology
Tammy Oth, Thomas H P M Habets, Wilfred T V Germeraad, Marijke I Zonneveld, Gerard M J Bos, Joris Vanderlocht
BACKGROUND: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus...
February 13, 2018: BMC Immunology
Sarah Jane Quillin, H Steven Seifert
The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N...
February 12, 2018: Nature Reviews. Microbiology
Ning Ma, Pingting Guo, Jie Zhang, Ting He, Sung Woo Kim, Guolong Zhang, Xi Ma
The intestine is the shared site of nutrient digestion, microbiota colonization and immune cell location and this geographic proximity contributes to a large extent to their interaction. The onset and development of a great many diseases, such as inflammatory bowel disease and metabolic syndrome, will be caused due to the imbalance of body immune. As competent assistants, the intestinal bacteria are also critical in disease prevention and control. Moreover, the gut commensal bacteria are essential for development and normal operation of immune system and the pathogens are also closely bound up with physiological disorders and diseases mediated by immune imbalance...
2018: Frontiers in Immunology
Ophélie Rouxel, Agnès Lehuen
Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant (MAI)T cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases...
February 6, 2018: Immunology and Cell Biology
Mark Bazett, Amanda M Costa, Momir Bosiljcic, Rebecca M Anderson, Matthew P Alexander, Stephanie W Y Wong, Salim Dhanji, Jenny Mh Chen, Jim Pankovich, Stephen Lam, Simon Sutcliffe, Hal Gunn, Shirin Kalyan, David W Mullins
Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity...
2018: Oncoimmunology
Michael Hecker, Ulrike Mäder, Uwe Völker
While the genome sequence is the blueprint of life, functional genomics is required to transfer the genome sequence to cell physiology. Among the Omics technologies, proteomics holds a privileged position because it deals with the main players of life, the proteins. For the model organism Staphylococcus aureus comprehensive coverage of the proteome was accomplished and used to address physiological and pathophysiological questions. This review article demonstrates that the proteomic view of physiology and pathophysiology of S...
January 5, 2018: International Journal of Medical Microbiology: IJMM
Khan Behlol Ayaz Ahmed, Thiagarajan Raman, Anbazhgan Veerappan
Bacterial resistance is a major clinical problem, which is compounded by both a lack of new antibiotics and emergence of multi- and extremely-drug resistant microbes. In this context, non-toxic nanoparticles could play an important role in conferring protection against bacterial infections and in this study we have made an attempt to show the usefulness of jacalin capped platinum nanoparticles in protecting zebrafish against multiple infections with Aeromonas hydrophila. Our results also indicate that use of nanoparticles promotes adaptive immune response against the pathogen, so much so that zebrafish is able to survive repetitive infection even after twenty one days of being treated with jacalin-capped platinum nanoparticles...
February 2, 2018: Scientific Reports
Akihiro Shimba, Guangwei Cui, Shizue Tani-Ichi, Makoto Ogawa, Shinya Abe, Fumie Okazaki, Satsuki Kitano, Hitoshi Miyachi, Hisakata Yamada, Takahiro Hara, Yasunobu Yoshikai, Takashi Nagasawa, Günther Schütz, Koichi Ikuta
Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in T cells, whether they control T cell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse T cells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday...
January 26, 2018: Immunity
Katia Troha, Joo Hyun Im, Jonathan Revah, Brian P Lazzaro, Nicolas Buchon
Host responses to infection encompass many processes in addition to activation of the immune system, including metabolic adaptations, stress responses, tissue repair, and other reactions. The response to bacterial infection in Drosophila melanogaster has been classically described in studies that focused on the immune response elicited by a small set of largely avirulent microbes. Thus, we have surprisingly limited knowledge of responses to infection that are outside the canonical immune response, of how the response to pathogenic infection differs from that to avirulent bacteria, or even of how generic the response to various microbes is and what regulates that core response...
February 2, 2018: PLoS Pathogens
Eleanor A Fallon, Bethany M Biron-Girard, Chun-Shiang Chung, Joanne Lomas-Neira, Daithi S Heffernan, Sean F Monaghan, Alfred Ayala
Coinhibitory molecules, such as PD-1, CTLA-4, 2B4, and BTLA, are an important new family of mediators in the pathophysiology of severe bacterial and/or fungal infection, as well as the combined insults of shock and sepsis. Further, the expression of these molecules may serve as indicators of the immune status of the septic individual. Using PD-1:PD-L as an example, we discuss in this review how such checkpoint molecules may affect the host response to infection by mediating the balance between effective immune defense and immune-mediated tissue injury...
February 2, 2018: Journal of Leukocyte Biology
P Mergaert
Covering: up to 2018Antimicrobial peptides (AMPs) have been known for well over three decades as crucial mediators of the innate immune response in animals and plants, where they are involved in the killing of infecting microbes. However, AMPs have now also been found to be produced by eukaryotic hosts during symbiotic interactions with bacteria. These symbiotic AMPs target the symbionts and therefore have a more subtle biological role: not eliminating the microbial symbiont population but rather keeping it in check...
February 2, 2018: Natural Product Reports
Barbara Reich, Susanne F Viehmann, Christian Kurts
Plasmacytoid dendritic cells are a unique dendritic cell subset that bridges innate and adaptive immune responses. They release high amounts of type I interferons in response to viral and bacterial infection. Plasmacytoid dendritic cells are thought to act as key players in renal allograft rejection, but the underlying mechanisms are unclear. Ruben et al. now demonstrate that granulocyte/macrophage colony-stimulating factor produced by renal epithelial cells is important to induce plasmacytoid dendritic cell maturation and indirect antigen presentation triggering allogeneic immune responses...
February 2018: Kidney International
Jeff Nivala, Seth L Shipman, George M Church
The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli...
January 29, 2018: Nature Microbiology
Yang Zhang, Jun Yang, Guangchun Bai
Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide an adaptive immunity to bacteria and archaea against specific DNA invaders. Mycobacterium tuberculosis (Mtb) encodes a Type III CRISPR-Cas system, which has not been experimentally explored. In this study, we found that the CRISPR-Cas systems of both Mtb and M. bovis BCG were highly upregulated by deletion of Rv2837c (cnpB), which encodes a multifunctional protein that hydrolyzes cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and nanoRNAs (short oligonucleotides of five residues or shorter in length)...
January 29, 2018: Journal of Bacteriology
Tao Wang, Gang Wang, Zhan-Hui Jia, De-Lin Pan, Ji-Yu Zhang, Zhong-Ren Guo
Kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has brought about a severe threat to the kiwifruit industry worldwide since its first outbreak in 2008. Studies on other pathovars of P. syringae are revealing the pathogenesis of these pathogens, but little about the mechanism of kiwifruit bacterial canker is known. In order to explore the species-specific interaction between Psa and kiwifruit, we analyzed the transcriptomic profile of kiwifruit infected by Psa. After 48 h, 8255 differentially expressed genes were identified, including those involved in metabolic process, secondary metabolites metabolism and plant response to stress...
January 26, 2018: International Journal of Molecular Sciences
Matthew Knight, Jonathan Braverman, Kaleb Asfaha, Karsten Gronert, Sarah Stanley
Lipid droplet (LD) formation occurs during infection of macrophages with numerous intracellular pathogens, including Mycobacterium tuberculosis. It is believed that M. tuberculosis and other bacteria specifically provoke LD formation as a pathogenic strategy in order to create a depot of host lipids for use as a carbon source to fuel intracellular growth. Here we show that LD formation is not a bacterially driven process during M. tuberculosis infection, but rather occurs as a result of immune activation of macrophages as part of a host defense mechanism...
January 25, 2018: PLoS Pathogens
Xiaoyu Pan, Desheng Gong, Duc Ninh Nguyen, Xinxin Zhang, Qi Hu, Hanlin Lu, Merete Fredholm, Per T Sangild, Fei Gao
Epigenetic regulation may play an important role in mediating microbe-host interactions and adaptation of intestinal gene expression to bacterial colonization just after birth. This is particularly important after preterm birth because the immature intestine is hypersensitive to invading bacteria. We compared the intestinal DNA methylome and microbiome between conventional (CON) and antibiotics-treated (AB) preterm pigs, used as a model for preterm infants. Oral AB treatment reduced bacterial density (∼100-fold), diversity and fermentation, improved the resistance to necrotizing enterocolitis (NEC) and changed the genome-wide DNA methylation in the distal small intestine...
January 19, 2018: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
J B Wechsler, A Szabo, C L Hsu, R A Krier-Burris, H A Schroeder, M Y Wang, R G Carter, T E Velez, L M Aguiniga, J B Brown, M L Miller, B K Wershil, T A Barrett, P J Bryce
Ulcerative colitis (UC) patients exhibit elevated histamine, but how histamine exacerbates disease is unclear as targeting histamine 1 receptor (H1R) or H2R is clinically ineffective. We hypothesized that histamine functioned instead through the other colon-expressed histamine receptor, H4R. In humans, UC patient biopsies exhibited increased H4R RNA and protein expression over control tissue, and immunohistochemistry showed that H4R was in proximity to immunopathogenic myeloperoxidase-positive neutrophils. To characterize this association further, we employed both the oxazolone (Ox)- and dextran sulfate sodium (DSS)-induced experimental colitis mouse models and also found upregulated H4R expression...
January 24, 2018: Mucosal Immunology
Lamia Harper, Divya Balasubramanian, Elizabeth A Ohneck, William E Sause, Jessica Chapman, Bryan Mejia-Sosa, Tenzin Lhakhang, Adriana Heguy, Aristotelis Tsirigos, Beatrix Ueberheide, Jeffrey M Boyd, Desmond S Lun, Victor J Torres
Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S...
January 23, 2018: MBio
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