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Infection and Immunity

Mancheong Ma, Daniel A Powell, Nathan J Weyand, Katherine A Rhodes, María A Rendón, Jeffrey A Frelinger, Magdalene So
Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization - and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, Neisseria musculi , with the laboratory mouse...
February 12, 2018: Infection and Immunity
Berglind Bergmann, Pernilla Jirholt, Petra Henning, Catharina Lindholm, Claes Ohlsson, Iain B McInnes, Ulf H Lerner, Inger Gjertsson
Background: Staphylococcus aureus -induced arthritis causes rapid joint destruction, often leading to disabling joint damage despite antibiotics. We have previously shown that IL-15 inhibition without antibiotics is beneficial in S. aureus -induced arthritis. We therefore hypothesized that inhibition of IL-15, in combination with antibiotics, might represent a useful therapy that would both reduce inflammation and joint destruction, but preserve the host's ability to clear the infection. Methods: Female wildtype C57BL/6 mice were intravenously inoculated with the TSST-1-producing LS-1 strain of S...
February 12, 2018: Infection and Immunity
Róisín M McMahon, Philip M Ireland, Derek S Sarovich, Guillaume Petit, Christopher H Jenkins, Mitali Sarkar-Tyson, Bart J Currie, Jennifer L Martin
The naturally antibiotic-resistant bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern Australia and Southeast Asia. Bacterial disulfide bond proteins (DSB) catalyze the oxidative folding and isomerization of disulfide bonds in substrate proteins. In the present study, we demonstrate that B...
February 12, 2018: Infection and Immunity
Lurdes Rodrigues-Duarte, Yash Pandya, Rita Neres, Carlos Penha-Gonçalves
Malaria in Pregnancy (MiP) is a distinctive clinical form of Plasmodium infection and is a cause of placental insufficiency leading to poor pregnancy outcomes of pregnancy Maternal innate immunity responses play a decisive role in the development of placental inflammation but the action of fetal-derived factors in MiP outcomes has been overlooked. We investigated the role of Tlr4 and Ifnar1 genes taking advantage of heterogenic mating strategies to dissect the effects mediated by maternal and fetal-derived TLR4 or IFNAR1...
February 12, 2018: Infection and Immunity
Guangping Huang, Sixin Zhang, Chunxue Zhou, Xiaoli Tang, Chao Li, Chaoyue Wang, Xinming Tang, Jingxia Suo, Yonggen Jia, El-Ashram Saeed, Zhengquan Yu, Jianping Cai, Nishith Gupta, Xun Suo, Xianyong Liu
Coccidiosis, caused by different species of Eimeria , is an economically important disease of poultry and livestock worldwide. Here, we report previously unknown alterations in gut microbes and metabolism of BALB/c mice infected with E. falciformis Specifically, we observed a significant shift in the abundance of cecal bacteria and disrupted metabolism in parasitized animals. Lachnospiraceae_NK4A136 , Ruminiclostridium , Alistipes , and Lactobacillus declined in response to E. falciformis infection, whereas Escherichia , Shigella , Helicobacter , Klebsiella and Bacteroides species increased...
February 12, 2018: Infection and Immunity
Ashley M Vaughan, Brandon K Sack, Dorender Dankwa, Nana Minkah, Thao Nguyen, Hayley Cardamone, Stefan H I Kappe
Genetically attenuated malaria parasites (GAP) that arrest during liver stage development are powerful immunogens and afford complete and durable protection against sporozoite infection. Late liver stage-arresting GAP provide superior protection against sporozoite challenge in mice when compared to early live stage-arresting attenuated parasites. However, very few late liver stage-arresting GAP have been generated to date. Therefore, identification of additional loci that are critical for late liver stage development and can be used to generate novel late liver stage-arresting GAPs are of importance...
February 12, 2018: Infection and Immunity
J M Sahler, C R Eade, C Altier, J C March
Non-typhoidal serovars of Salmonella enterica are pathogenic bacteria that are common causes of food poisoning. Whereas Salmonella mechanisms of host cell invasion, inflammation, and pathogenesis are mostly well-established, a new possible mechanism of immune evasion is being uncovered. PD-L1 is an immunosuppressive membrane protein that binds to activated T cells via their PD-1 receptor and thereby halts their activation. PD-L1 expression plays an essential role in immunological tolerance of self, but is also exploited for immune evasion by pathogen-infected cells and cancer cells...
February 12, 2018: Infection and Immunity
Wen Wen, Banghui Liu, Lu Xue, Zhongliang Zhu, Liwen Niu, Baolin Sun
Toxin-antitoxin (TA) systems play diverse physiological roles such as plasmid maintenance, growth control, and persister cell formation, but their involvement in bacterial pathogenicity remains largely unknown. Here we have identified a novel type II toxin-antitoxin system SavRS and revealed the molecular mechanisms of its autoregulation and virulence control in Staphylococcus aureus. Electrophoretic mobility shift assay and isothermal titration calorimetry data indicated that the antitoxin SavR acted as the primary repressor bound to its own promoter, while the toxin SavS formed a complex with SavR to enhance the binding ability to the operator site...
February 12, 2018: Infection and Immunity
Dong-Wook Hyun, Hyun Jin Min, Min-Soo Kim, Tae Woong Whon, Na-Ri Shin, Pil Soo Kim, Hyun Sik Kim, June Young Lee, Woorim Kang, Augustine M K Choi, Joo-Heon Yoon, Jin-Woo Bae
Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, inferior turbinate, in subjects with allergic rhinitis (n=20) and healthy controls (n=12), and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, allergen-specific- and total-IgE levels...
February 5, 2018: Infection and Immunity
Masoud Akbari, Kazumi Kimura, Ganchimeg Bayarsaikhan, Daisuke Kimura, Mana Miyakoda, Smriti Juriasingani, Masao Yuda, Rogerio Amino, Katsuyuki Yui
CD8+ T cells are the major effector cells that protect against malaria liver-stage infection, forming clusters around Plasmodium-infected hepatocytes and eliminating parasites after prolonged interaction with these hepatocytes. We aimed to investigate roles of specific and non-specific CD8+ T cells in cluster formation and protective immunity. To this end, we used Plasmodium berghei ANKA expressing ovalbumin, as well as CD8+ T cells from transgenic mice expressing a T cell receptor specific for ovalbumin (OT-I) and CD8+ T cells specific for an unrelated antigen, respectively...
February 5, 2018: Infection and Immunity
Rebecca W Olsen, Gertrude Ecklu-Mensah, Anja Bengtsson, Michael F Ofori, John P A Lusingu, Filip C Castberg, Lars Hviid, Yvonne Adams, Anja T R Jensen
Cerebral malaria (CM) is a potentially deadly outcome of Plasmodium falciparum malaria that is precipitated by sequestration of infected erythrocytes (IEs) in the brain. The adhesion of IEs to brain endothelial cells is mediated by a subtype of parasite-encoded PfEMP1 that facilitate dual binding to host ICAM-1 and EPCR. The PfEMP1 subtype is characterized by the presence of a particular motif (DBLβ_motif) in the constituent ICAM-1-binding DBLβ domain. The rate of natural acquisition of DBLβ_motif-specific IgG and the ability to induce such antibodies by vaccination are unknown, and the aim of this study was to provide such data...
February 5, 2018: Infection and Immunity
C A Naranjo-Galvis, A de-la-Torre, L E Mantilla-Muriel, L Beltrán-Angarita, X Elcoroaristizabal-Martín, R McLeod, N Alliey-Rodriguez, I J Begeman, C López de Mesa, J E Gómez-Marín, J C Sepúlveda-Arias
Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population, however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for cytokines TNF-α (rs1799964, rs1800629, rs1799724, rs1800630, rs361525); IL-1β (rs16944, rs1143634, rs1143627), IL-1α (rs1800587); IFN-γ (rs2430561); IL-10 (rs1800896, rs1800871), and the presence of ocular toxoplasmosis (OT) in a sample of Colombian population (61 patients with OT and 116 healthy controls)...
February 5, 2018: Infection and Immunity
Michelle G Pitts, Travis A Combs, Sarah E F D'Orazio
Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (PMN) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly kill L. monocytogenes has not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and both cell types readily migrated towards leukotriene B4 in an in vitro chemotaxis assay...
February 5, 2018: Infection and Immunity
Laura C Cook, Hong Hu, Mark Maienschein-Cline, Michael J Federle
Streptococcus agalactiae (Group B Streptococcus, GBS) can colonize the human vaginal tract leading to both superficial and serious infections in adults and neonates. To study bacterial colonization of the reproductive tract in a mammalian system, we employ a murine vaginal carriage model. Using RNASeq, the transcriptome of GBS growing in vivo during vaginal carriage was determined. Over one-quarter of the genes in GBS are found to be differentially regulated during in vivo colonization as compared to laboratory cultures...
January 29, 2018: Infection and Immunity
Erika van der Maten, Bryan van den Broek, Marien I de Jonge, Kim J W Rensen, Marc J Eleveld, Aldert L Zomer, Amelieke J H Cremers, Gerben Ferwerda, Ronald de Groot, Jeroen D Langereis, Michiel van der Flier
Pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown...
January 29, 2018: Infection and Immunity
Kenneth Gavina, Sedami Gnidehou, Eliana Arango, Chloe Hamel-Martineau, Catherine Mitran, Olga Agudelo, Carolina Lopez, Aisha Karidio, Shanna Banman, Jaime Carmona-Fonseca, Ali Salanti, Nicaise Ndam, Michael Hawkes, Amanda Maestre, Stephanie K Yanow
BACKGROUND: Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate. METHODS: A cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology...
January 29, 2018: Infection and Immunity
J Wendler, D Ehmann, L Courth, B O Schroeder, N P Malek, J Wehkamp
The antimicrobial peptide human ß-defensin 1 (hBD1) is continuously produced by epithelial cells in many tissues. Compared to other defensins, hBD1 has only minor antibiotic activity in its native state. After reduction of its disulfide bridges, however, it becomes a potent antimicrobial agent against bacteria, while the oxidized native form (hBD1ox) shows specific activity against Gram-negative bacteria. We show that the killing mechanism of hBD1ox depends on aerobic growth conditions and bacterial enzymes...
January 29, 2018: Infection and Immunity
Chi Yong Kim, Xuejin Zhang, William H Witola
Rats vary in their susceptibilities to Toxoplasma gondii infection depending on the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to T. gondii infection. Therefore, in our efforts to unravel molecular factors directing the protective early innate immune response in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T...
January 29, 2018: Infection and Immunity
Suhanya Duraiswamy, Jacqueline L Y Chee, Siyi Chen, Enjun Yang, Kristin Lees, Swaine L Chen
Urinary tract infections (UTIs) are a major infection of humans, particularly affecting women. Recurrent UTIs can cause significant discomfort and expose patients to high levels of antibiotic use, in turn contributing to the development of higher antibiotic resistance rates. Most UTIs are caused by uropathogenic Escherichia coli , which are able to form intracellular collections (termed intracellular bacterial communities (IBCs)) within the epithelial cells lining the bladder lumen. IBCs are seen in both infected mice and humans and are a potential cause for recurrent UTI...
January 29, 2018: Infection and Immunity
Matthew N Neale, Kyle A Glass, Sarah J Longley, Denny J Kim, Sonia S Laforce-Nesbitt, Jeremy D Wortzel, Sunil K Shaw, Joseph M Bliss
The yeast, Candida parapsilosis, is an increasingly common cause of systemic fungal infections among the immune compromised, including premature infants. Adhesion to host surfaces is an important step in pathogenesis, but this process has not been extensively studied in this organism. A microfluidics assay was developed to test the ability of C. parapsilosis to adhere to immobilized host extracellular matrix proteins under physiologic fluid shear conditions. Growth in mammalian tissue culture media at 37°C for 3-6 hours led to induction of an adhesive phenotype at shear forces of 1-5 dynes/cm2 in some isolates of C...
January 29, 2018: Infection and Immunity
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