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Infection and Immunity

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https://www.readbyqxmd.com/read/29203548/utilization-of-host-polyamines-in-alternatively-activated-macrophages-promotes-chronic-infection-by-brucella-abortus
#1
Tobias Kerrinnes, Maria G Winter, Briana M Young, Vladimir E Diaz-Ochoa, Sebastian E Winter, Renée M Tsolis
Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple antibiotics. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAM), however knowledge of the metabolic adaptations promoting exploitation of this niche is limited...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203547/regulated-release-of-cryptococcal-polysaccharide-drives-virulence-and-suppresses-immune-infiltration-into-the-central-nervous-system
#2
Steven T Denham, Surbhi Verma, Raymond C Reynolds, Colleen L Worne, Joshua M Daugherty, Thomas E Lane, Jessica C S Brown
Cryptococcus neoformans is a common environmental yeast and opportunistic pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality primarily results from meningoencephalitis, which occurs when fungal cells disseminate to the brain from the initial pulmonary infection site. A key C. neoformans virulence trait is the polysaccharide capsule. Capsule shields C. neoformans from immune-mediated recognition and destruction. The main capsule component, glucuronoxylomannan (GXM), is found both attached to the cell surface and free in the extracellular space (as exo-GXM)...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203546/use-of-proteins-identified-through-a-functional-genomic-screen-to-develop-a-protein-subunit-vaccine-that-provides-significant-protection-against-virulent-streptococcus-suis-in-pigs
#3
Susan L Brockmeier, Crystal L Loving, Tracy L Nicholson, Jinhong Wang, Sarah E Peters, Lucy Weinert, Roy Chaudhuri, David J Seilly, Paul R Langford, Andrew Rycroft, Brendan W Wren, Duncan J Maskell, Alexander W Tucker
Streptococcus suis is a bacterium commonly carried in the respiratory tract that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203545/bordetella-pertussis-adenylate-cyclase-toxin-disrupts-functional-integrity-of-bronchial-epithelial-layers
#4
Shakir Hasan, Nikhil Nitin Kulkarni, Arni Asbjarnarson, Irena Linhartova, Radim Osicka, Peter Sebo, Gudmundur H Gudmundsson
Airway epithelium restricts penetration of inhaled pathogens into the underlying tissue and plays a crucial role in innate immune defense against respiratory infections. The whooping cough agent, Bordetella pertussis, adheres to ciliated cells of human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We have examined the impact of B. pertussis infection and of adenylate cyclase toxin (CyaA) action on the functional integrity of air-liquid interface (ALI)-cultured human bronchial epithelial cells...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203544/mapping-protective-regions-on-a-three-dimensional-model-of-the-moraxella-catarrhalis-vaccine-antigen-oligopeptide-permease-a
#5
Antonia C Perez, Antoinette Johnson, Ziqiang Chen, Gregory E Wilding, Michael G Malkowski, Timothy F Murphy
A vaccine against Moraxella catarrhalis will reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of COPD in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is 1) a nutritional virulence factor expressed on the bacterial cell surface during infection, 2) widely conserved among strains, 3) highly immunogenic, and 4) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals following pulmonary challenge...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203543/a-novel-mechanism-behind-the-immunopathogenesis-of-vulvovaginal-candidiasis-neutrophil-anergy
#6
Junko Yano, Brian M Peters, Mairi C Noverr, Paul L Fidel
For over three decades, investigators have studied the pathogenesis of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal models. While there was considerable consensus that susceptibility was not associated with any apparent deficiencies in adaptive immunity, protective immune mechanisms and the role of innate immunity remained elusive. It was not until an innovative live challenge design was conducted in women that a fuller understanding of the natural history of infection/disease was achieved...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203542/pro-inflammatory-role-of-monocyte-derived-cx3cr1int-macrophages-in-helicobacter-hepaticus-induced-colitis
#7
Calum C Bain, Christopher J Oliphant, Carolyn A Thomson, Marika C Kullberg, Allan McI Mowat
Cells of the monocyte-macrophage lineage play important roles in the pathogenesis of inflammatory bowel diseases, but they are also present in the normal healthy intestine, where they are critical for maintaining homeostasis. It has been unclear whether the pro-inflammatory roles of intestinal macrophages reflect altered behaviour of the existing resident cells, or if they involve recruitment of a distinct cell type. Here we have explored these ideas using the model of colitis induced by Helicobacter hepaticus (Hh) in the context of neutralisation or deletion of interleukin 10 (IL-10)...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203541/nani-sialidase-can-support-the-growth-and-survival-of-clostridium-perfringens-strain-f4969-using-sialyated-host-macromolecules-mucin-or-caco-2-cells
#8
Jihong Li, Bruce A McClane
Enterotoxin-producing Clostridium perfringens type A strains cause human gastrointestinal (GI) infections, including a very common food poisoning and 5-10% of all antibiotic-associated diarrhea cases. This bacterium can utilize free sialic acid for growth but most sialic acids in the GI tract are sequestered on macromolecules such as the mucin proteins of mucus or glycoconjugates in host cells. However, many C. perfringens strains produce sialidases that might promote growth and survival by generating free sialic acid from those sialyated host macromolecules or by exposing underlying carbohydrates or proteins for digestion by other enzymes...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203540/toward-tuberculosis-vaccine-development-recommendations-for-nhp-study-design
#9
Dominick J Laddy, Aurelio Bonavia, Willem A Hanekom, Deepak Kaushal, Ann Williams, Mario Roederer, Robert A Seder, Sally Sharpe, Frank A W Verreck, Patricia A Darrah
Clinical trials of novel tuberculosis vaccines are expensive, while global resources for TB vaccine development are limited. There is therefore a need for robust and predictive pre-clinical data to support advancement of candidate vaccines into clinical trials. Here, we provide a rationale for using the nonhuman primate as an essential component of these efforts, as well as guidance to the TB community for standardizing experimental design and aligning endpoints to facilitate development of new TB vaccines.
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158434/high-levels-of-cyclic-di-gmp-in-klebsiella-pneumoniae-attenuate-virulence-in-the-lung
#10
David A Rosen, Joy Twentyman, David A Hunstad
The bacterial second messenger, bis-(3' -5')-cyclic dimeric guanosine monophosphate (c-di-GMP) has been shown to influence expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogen Klebsiella pneumoniae Here, expression in K. pneumoniae of a heterologous diguanylate cyclase increased bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident in mice lacking the c-di-GMP sensor STING, indicating that high c-di-GMP exerted its influence not on host responses, but on bacterial physiology...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158433/whole-genome-characterization-of-bacillus-cereus-associated-with-specific-disease-manifestations
#11
T Chang, J W Rosch, Z Gu, H Hakim, C Hewitt, A Gaur, G Wu, R T Hayden
Bacillus cereus remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding we undertook whole genome analysis of B. cereus strains isolated from patients with a range of disease manifestations, including non-invasive colonizing disease, superficial skin infections, and invasive bacteremia...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158432/identification-and-characterization-of-serotype-specific-variation-in-group-a-streptococcus-pilus-expression
#12
Gregory Calfee, Jessica L Danger, Ira Jain, Eric W Miller, Poulomee Sarkar, Brian Tjaden, Bernd Kreikemeyer, Paul Sumby
Isolates of a given bacterial pathogen often display phenotypic variation, and this can negatively impact public health, for example by reducing the efficacy of preventative measures. Here, we identify that the human pathogen group A Streptococcus (GAS; Streptococcus pyogenes) expresses pili on its cell surface in a serotype-specific manner. Specifically, we show that serotype M3 GAS isolates, which are non-randomly associated with causing particularly severe and lethal invasive infections, produce negligible amounts of pili relative to serotype M1 and M49 isolates...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158431/salmonella-typhimurium-alters-the-extracellular-proteome-of-macrophages-and-leads-to-the-production-of-pro-inflammatory-exosomes
#13
Winnie W Hui, Kamil Hercik, Sayali Belsare, Navatha Alugubelly, Beata Clapp, Carlos Rinaldi, Mariola J Edelmann
Salmonella enterica serovar Typhimurium is a Gram-negative bacterium, which can invade and survive within macrophages. Pathogenic Salmonellae induce the secretion of specific cytokines from these phagocytic cells and interfere with the host secretory pathways. In this study, we describe the extracellular proteome of human macrophages infected with S. Typhimurium, followed by analysis of canonical pathways of proteins isolated from the extracellular milieu. We demonstrate that some of the proteins secreted by macrophages upon S...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158430/characterization-of-stress-and-innate-immunity-resistance-of-wild-type-and-%C3%AE-p66-borrelia-burgdorferi
#14
Michael W Curtis, Beth L Hahn, Kai Zhang, Chunhao Li, Richard T Robinson, Jenifer Coburn
Borrelia burgdorferi is a causative agent of Lyme disease, the most common arthropod-borne disease in the United States. B. burgdorferi evades host immune defenses to establish a persistent, disseminated infection. Previous work showed that P66-deficient B. burgdorferi (Δp66) is cleared quickly after inoculation in mice. We demonstrate that Δp66 is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of Δp66 is not due to inherent defects in multiple properties that might affect infectivity: bacterial outer membrane integrity, motility, chemotactic response, or nutrient acquisition...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158429/b-cell-presentation-of-chlamydia-antigen-selects-out-protective-cd4%C3%AE-13-t-cells-implications-for-genital-tract-tissue-resident-memory-lymphocyte-clusters
#15
Raymond M Johnson, Hong Yu, Norma Olivares Strank, Karuna Karunakaran, Ying Zhu, Robert C Brunham
Surveillance and defense of the enormous mucosal interface with the nonsterile world is critical to protecting the host from a wide range of pathogens. Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract. The fallopian tubes and vagina are poorly suited to surveillance and defense with limited immune infrastructure positioned near the epithelium. However, a dynamic process during clearing primary infections leaves behind new lymphoid clusters immediately beneath the epithelium...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158428/borrelia-burgdorferi-glycosaminoglycan-binding-protein-bgp-in-the-b31-strain-is-not-essential-for-infectivity-despite-facilitating-adherence-and-tissue-colonization
#16
Samantha Schlachter, Janakiram Seshu, Tao Lin, Steven Norris, Nikhat Parveen
Lyme disease causing Borrelia burgdorferi is transmitted into the mammalian host by an infected tick bite. Successful infection relies on the ability of this extracellular pathogen to persist and colonize different tissues. B. burgdorferi encodes a large number of adhesins that are able to interact with host ligands to facilitate adherence, and tissue colonization. Multiple glycosaminoglycan binding proteins presence in B. burgdorferi offer a degree of redundancy of function during infection, and highlights the importance for glycosaminoglycans as host cell receptors for spirochete adherence...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133349/the-role-of-calprotectin-in-withholding-zinc-and-copper-from-candida-albicans
#17
Angelique N Besold, Benjamin A Gilston, Jana N Radin, Christian Ramsoomair, Edward M Culbertson, Cissy X Li, Brendan P Cormack, Walter J Chazin, Thomas E Kehl-Fie, Valeria C Culotta
The opportunistic fungal pathogen Candida albicans acquires essential metals from the host, yet the host can sequester these micronutrients through a process known as nutritional immunity. How the host withholds metals from C. albicans was poorly understood and here we examine the role of calprotectin (CP), a transition metal binding protein. When CP depletes bioavailable Zn from the extracellular environment, C. albicans strongly upregulates ZRT1 and PRA1 for Zn import and maintains constant intracellular Zn through numerous cell divisions...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133348/non-pathogenic-colonization-with-chlamydia-in-the-gastrointestinal-tract-as-oral-vaccination-for-inducing-transmucosal-protection
#18
Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital infection and stronger protection against subsequent genital tract challenge infection. Mice pre-inoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133347/analysis-of-the-human-mucosal-response-to-cholera-reveals-sustained-activation-of-innate-immune-signaling-pathways
#19
Daniel L Bourque, Taufiqur Rahman Bhuiyan, Diane P Genereux, Rasheduzzaman Rashu, Crystal N Ellis, Fahima Chowdhury, Ashraful I Khan, Nur Haq Alam, Anik Paul Lazina Hossain, Leslie M Mayo-Smith, Richelle C Charles, Ana A Weil, Regina C LaRocque, Stephen B Calderwood, Edward T Ryan, Elinor K Karlsson, Firdausi Qadri, Jason B Harris
To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133346/mycobacterium-tuberculosis-groel2-modulates-dendritic-cell-responses
#20
Maria Georgieva, Jonathan Kevin Sia, Erica Bizzell, Ranjna Madan-Lala, Jyothi Rengarajan
Mycobacterium tuberculosis (Mtb) successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, Mtb interferes with the functions of dendritic cells (DCs), which are the primary antigen presenting cells in the immune system. We previously showed that Mtb dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease, Hip1. Here we present data showing that Mtb GroEL2, a substrate of Hip1, modulates DC functions...
November 13, 2017: Infection and Immunity
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