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Infection and Immunity

Nina M Poole, Sabrina I Green, Anubama Rajan, Luz E Vela, Xi-Lei Zeng, Mary K Estes, Anthony W Maresso
The translocation of bacteria across the intestinal epithelium of immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal Pathogenic Escherichia coli (ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon...
August 14, 2017: Infection and Immunity
Jana Neiman-Zenevich, Sarah Stuart, Mena Abdel-Nour, Stephen E Girardin, Jeremy Mogridge
Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might, therefore, sense microbial infection as intracellular pathogens such as Listeria monocytogenes and Shigella flexneri cause metabolic stress as a result of nutrient scavenging and host cell damage...
August 14, 2017: Infection and Immunity
David Corbett, Marie Goldrick, Vitor E Fernandes, Kelly Davidge, Robert K Poole, Peter W Andrew, Jennifer Cavet, Ian S Roberts
Listeria monocytogenes is a food borne pathogen responsible for a number of life-threatening infections of humans. During an infection it invades epithelial cells before spreading from the intestine to the cells of the liver and spleen. This requires an ability to adapt to varying oxygen levels. Here we demonstrate that L. monocytogenes has two terminal oxidases, a cytochrome bd-type (CydAB) and a cytochrome aa3 -type menaquinol oxidase (QoxAB) and that both are used for respiration under different oxygen tensions...
August 14, 2017: Infection and Immunity
Candace N Rouchon, Anhphan T Ly, John P Noto, Feng Luo, Sergio Lizano, Debra E Bessen
Group A streptococci (GAS) are highly prevalent human pathogens whose primary ecological niche is the superficial epithelial layers of the throat and/or skin. Many GAS strains having a strong tendency to cause pharyngitis are distinct from strains that tend to cause impetigo; thus, genetic differences between them may confer host tissue-specific virulence. In this study, the FbaA surface protein gene is found to be present in most skin specialist strains, but largely absent from a genetically-related subset of pharyngitis isolates...
August 14, 2017: Infection and Immunity
Arnaud Machelart, Abir Khadrawi, Aurore Demars, Kevin Willemart, Carl De Trez, Jean-Jacques Letesson, Eric Muraille
The spleen is known as an important filter for blood-borne pathogens that are trapped by specialized macrophages in the marginal zone (MZ): the CD209(+) MZ macrophages (MZMs) and the CD169(+) marginal metallophilic macrophages (MMMs). Acute systemic infection strongly impacts MZ populations and the location of T and B lymphocytes. This phenomenon has been linked to reduced chemokine secretion by stromal cells. Brucella spp. are the causative agent of brucellosis, a widespread zoonotic disease. Here, we used B...
August 14, 2017: Infection and Immunity
Zifeng Han, Thomas Willer, Li Li, Colin Pielsticker, Ivan Rychlik, Philippe Velge, Bernd Kaspers, Silke Rautenschlein
Campylobacter jejuni (C. jejuni)-host-interaction may be affected by the host's gut microbiota through competitive exclusion, metabolites or modification of the immune response. To understand this interaction C. jejuni colonization and local immune responses were compared in chickens with different gut microbiota composition. Birds were treated with an antibiotic cocktail (AT) (Experiment 1 and 2) or raised under germ-free (GF) conditions (Experiment 3). At 18 days post hatch (dph), they were either orally inoculated with 10(4) colony forming units (CFU) of C...
August 14, 2017: Infection and Immunity
Rudra Bhowmick, Stacie Clark, Joseph V Bonventre, John M Leong, Beth A McCormick
Pulmonary infection by Streptococcus pneumoniae is characterized by a robust alveolar infiltration of neutrophils (polymorphonuclear cells or PMNs) that can promote systemic spread of the infection if not resolved. We previously showed that 12-lipoxygenase (12-LOX), which is required to generate the PMN chemoattractant hepoxilin A3 (HXA3) from arachidonic acid (AA), promotes acute pulmonary inflammation and systemic infection after lung challenge with S. pneumoniae As phospholipase A2 (PLA2) promotes the release of AA, we investigated the role of PLA2 in local and systemic disease during S...
August 14, 2017: Infection and Immunity
John Connolly, Emma Boldock, Lynne R Prince, Stephen A Renshaw, Moira K Whyte, Simon J Foster
Staphylococcus aureus is a human commensal but also has devastating potential as an opportunist pathogen. S. aureus bacteraemia is often associated with an adverse outcome. To identify potential targets for novel control approaches we have identified S. aureus components that are required for growth on human blood. An ordered transposon mutant library was screened, identifying 9 genes involved specifically in haemolysis or growth on human blood agar compared to the parental strain. Three genes (purA, purB and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model...
August 14, 2017: Infection and Immunity
Ira Jain, Eric W Miller, Jessica L Danger, Kathryn J Pflughoeft, Paul Sumby
Regulating gene expression during infection is critical to the ability of pathogens to circumvent the immune response and cause disease. This is true for the group A Streptococcus (GAS), a pathogen that causes both invasive (e.g. necrotizing fasciitis) and non-invasive (e.g. pharyngitis) diseases. The control of virulence (CovR/S) two-component system has a major role in regulating GAS virulence factor expression. The regulator of cov (RocA) protein, which is a predicted kinase, functions in an undetermined manner through CovR/S to alter gene expression and reduce invasive disease virulence...
August 14, 2017: Infection and Immunity
Karen M Scanlon, Yael G Snyder, Ciaran Skerry, Nicholas H Carbonetti
In infants, Bordetella pertussis can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension and even death. The exact cause of death remains unknown and no effective therapies exist for treating fulminant pertussis. In this study, a neonatal mouse model of critical pertussis is characterized and a central role for pertussis toxin (PT) is described. PT promoted colonization, leukocytosis, T cell phenotypic changes, systemic pathology and death in neonatal but not adult mice. Surprisingly, PT inhibited lung inflammatory pathology in neonates, a result which contrasts dramatically with observed PT-promoted pathology in adult mice...
August 7, 2017: Infection and Immunity
Xin Shi, Yuan-Ping Lin, Bin Gao, Ping Zhang
Alcohol abuse impairs immune defense. To study the effect of chronic-plus-binge alcohol exposure on the granulopoietic response, acute alcohol intoxication (intraperitoneal injection of 5g alcohol/kg body weight) was introduced to mice chronically fed on the Lieber-DeCarli low fat liquid alcohol diet for 5 weeks. Bacteremia was induced by intravenous injection of Escherichia coli Bacteremia caused a remarkable increase in marrow lin(-)c-kit(+)Sca-1(+) cells. Activation of cell proliferation supported the increase in marrow lin(-)c-kit(+)Sca-1(+) cells...
August 7, 2017: Infection and Immunity
Erin E Zwack, Eric Feeley, Amanda R Burton, Baofeng Hu, Masahiro Yamamoto, Thirumala-Devi Kanneganti, James B Bliska, Jörn Coers, Igor E Brodsky
Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by Nucleotide Binding Domain and Leucine Rich Repeat containing proteins (NLRs), which trigger formation of a multi-protein complex called the inflammasome, leading to secretion of IL-1 family cytokines, pyroptosis, and control of pathogen replication...
August 7, 2017: Infection and Immunity
Einat Nissim-Eliraz, Eilam Nir, Irit Shoval, Noga Marsiano, Israel Nissan, Hadar Shemesh, Nandor Nagy, Allan M Goldstein, Michael Gutnick, Ilan Rosenshine, Simcha Yagel, Nahum Y Shpigel
Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS) causing the hallmark lesions of attaching and effacing (AE) and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models. We therefore established an EPEC infection model in human gut xenografts in SCID mice and used it to study the role of T3SS in the pathogenesis of the disease...
August 7, 2017: Infection and Immunity
Christianne Maria Tinoco-Veras, Ana Angélica Q A Santos, Joice Stipursky, Marcelo Meloni, Ana Paula Bérgamo Araujo, Danielle Abreu Foschetti, Diana-López Ureña, Carlos Quesada-Gómez, Renata F C Leitão, Flávia Carvalho Alcantara Gomes, Gerly Anne de Castro Brito
Clostridium difficile, the main cause of diarrhea in hospitalized patients, produces toxins A (TcdA) and B (TcdB), which affect intestinal epithelial cell survival, proliferation, and migration, and induce an intense inflammatory response. TGF-β is a pleiotropic cytokine affecting enterocyte and immune/inflammatory responses. However, it has been shown that exposure of intestinal epithelium to a low concentration of TcdA induces the release of TGF-β1, which has a protective effect on epithelial resistance and a TcdA/TGF-β signaling pathway interaction...
August 7, 2017: Infection and Immunity
Marta Bacconi, Andreas F Haag, Emiliano Chiarot, Paolo Donato, Fabio Bagnoli, Isabel Delany, Giuliano Bensi
Staphylococcus aureus is an opportunistic human pathogen and a major cause of invasive infections such as bacteremia, endocarditis, pneumonia and wound infections. FhuD2 is a staphylococcal lipoprotein involved in the uptake of iron-hydroxymate and is under the control of the iron uptake regulator Fur. The protein is part of an investigational multi-component vaccine formulation that has shown protective efficacy in several murine models of infection. Even though fhuD2 expression was shown to be upregulated in murine kidneys infected with S...
August 7, 2017: Infection and Immunity
Junko Kido, Takaaki Shimohata, Sachie Amano, Syo Hatayama, Anh Quoc Nguyen, Yuri Sato, Yuna Kanda, Aya Tentaku, Shiho Fukushima, Mutsumi Nakahashi, Takashi Uebanso, Kazuaki Mawatari, Akira Takahashi
Campylobacter jejuni (C. jejuni) is gastroenteritis inducible food-born pathogen. Invasion and adhesion process are essential for leading gastroenteritis in C. jejuni infection process. As against bacterial strategy for efficacy invasion and adhesion, mucosal layer play a key role in defense systems, which modulated by several ion channels and transporters mediated water flux on the intestine. Cystic fibrosis transmembrane conductance regulator (CFTR) play the main role in waterfulux in intestine, and it closely related with bacterial clearance...
August 7, 2017: Infection and Immunity
Shadaan Abid, ShangKui Xie, Moumita Bose, Philip W Shaul, Lance S Terada, Steven L Brody, Philip J Thomas, John A Katzenellenbogen, Sung Hoon Kim, David E Greenberg, Raksha Jain
Rationale: Females have a more severe clinical course than males in several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of Pseudomonas aeruginosa infection. Sex hormones are implicated in experimental and clinical studies, however immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified.Objectives: Assess mechanisms behind the impact of female sex hormones on host immune responses to P...
August 7, 2017: Infection and Immunity
Wei Wang, Yue Shao, Shengjun Li, Na Xin, Tingxian Ma, Chenghai Zhao, Min Song
Activation of caspase-11 by some gram negative bacteria triggers caspase-1/IL-1β pathway independent of canonical inflammasomes. Acinetobacter baumannii (A. baumannii) are gram negative, conditional pathogenic bacteria, which can lead to severe pulmonary infection in hospitalized patients. A. baumannii were revealed to activate canonical and noncanonical inflammasome pathway in bone marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11(-/-) mice with A. baumannii showed that caspase-11 deficiency impaired A...
July 31, 2017: Infection and Immunity
Hubertine M E Willems, Winter S Bruner, Katherine S Barker, Junyan Liu, Glen E Palmer, Brian M Peters
The secreted aspartyl protineases of C. albicans have long been implicated in virulence at the mucosal surface, including contribution to colonization and immunopathogenesis during vulvovaginal candidiasis. In an effort to disentangle hypha-associated virulence factor regulation from morphological transition, the purpose of this study was to determine if overexpression of SAP2 or SAP5 in a efg1Δ/Δ/cph1Δ/Δ mutant could restore capacity to cause immunopathology during murine vaginitis to this avirulent hypofilamentous strain...
July 31, 2017: Infection and Immunity
Jennifer K Spinler, Jennifer Auchtung, Aaron Brown, Prapaporn Boonma, Numan Oezguen, Caná L Ross, Ruth Ann Luna, Jessica Runge, James Versalovic, Alex Peniche, Sara M Dann, Robert A Britton, Anthony Haag, Tor C Savidge
Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden to antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where rational design of next generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant CDI antibiotics (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri as a promising candidate for adjunct therapy...
July 31, 2017: Infection and Immunity
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