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Infection and Immunity

Annabel S Hinderfeld, Niha Phukan, Ann-Katrein Bär, Anthony M Roberton, Augusto Simoes-Barbosa
The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardenerella vaginalis , Atopobium vaginae and Prevotella bivia ). Both diseases are linked to the transmission of the Human Immunodeficiency Virus and preterm birth, which complications are likely to result from the disruption of the vaginal epithelial barrier...
March 11, 2019: Infection and Immunity
Tianyuan Zhang, Zhi Huo, Jingyue Ma, Cheng He, Guangming Zhong
Although Chlamydia trachomatis is a human genital tract pathogen, chlamydial organisms have been frequently detected in both vaginal and rectal swabs of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for C. muridarum to colonize mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization of pGP3-deficient C. muridarum mutant, suggesting that pGP3 is required for C. muridarum to reach but not colonize the large intestine...
March 11, 2019: Infection and Immunity
Andrew L Garfoot, Patrick W Cervantes, Laura J Knoll
The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. RNA-seq analysis previously determined that the host response in the brain was higher and more complex at 28 versus 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex- matched mice during very early (21 days), early (28 days), mid (3 months) and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased 6 months postinfection for both male and female mice...
March 11, 2019: Infection and Immunity
Amanda L Dragan, Richard C Kurten, Daniel E Voth
Human Q fever is caused by the intracellular bacterial pathogen Coxiella burnetii Q fever presents with acute flu-like and pulmonary symptoms or can progress to chronic, severe endocarditis. After human inhalation, C. burnetii is engulfed by alveolar macrophages and transits through the phagolysosomal maturation pathway, resisting lysosomal acidic pH to form a parasitophorous vacuole (PV) in which to replicate. Previous studies showed that C. burnetii replicates efficiently in primary human alveolar macrophages (hAMs) in ex vivo human lung tissue...
March 4, 2019: Infection and Immunity
Louise A Rollins-Smith, Antonio C Ruzzini, J Scott Fites, Laura K Reinert, Emily M Hall, Bryan A Joosse, Vishvaas I Ravikumar, Megan I Huebner, Audrey Aka, Miles H Kehs, Bria M Gillard, Emily Doe, Julia A Tasca, Thomas P Umile, Jon Clardy, Kevin P C Minbiole
Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus, Batrachochytrium dendrobatidis , which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis , but the fungus also has a number of counter-defenses. Previously, we identified two small molecules produced by this fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B...
March 4, 2019: Infection and Immunity
Zachary N Phillips, Charles Brizuela, Amy V Jennison, Megan Staples, Keith Grimwood, Kate L Seib, Michael P Jennings, John M Atack
Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing world-wide. NTHi is able to colonise the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease are not understood. We have previously reported that phase-variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonising the nasopharynx to invading the middle ear...
March 4, 2019: Infection and Immunity
Liliane Mukaremera, Tami R McDonald, Judith N Nielsen, Christopher J Molenaar, Andrew Akampurira, Charlotte Schutz, Kabanda Taseera, Conrad Muzoora, Graeme Meintjes, David B Meya, David R Boulware, Kirsten Nielsen
Cryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with clinical outcome but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with C. neoformans strains with the same multi-locus sequence type (MLST)...
March 4, 2019: Infection and Immunity
Stephanie Marroquin, Brittney Gimza, Brooke Tomlinson, Michelle Stein, Andrew Frey, Rebecca A Keogh, Rachel Zapf, Daniel A Todd, Nadja B Cech, Ronan K Carroll, Lindsey N Shaw
Numerous factors have to date been identified as playing a role in the regulation of Agr activity in S. aureus , including transcription factors, antisense RNAs, and host elements. Herein we investigate the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant we observed a drastic reduction in proteolysis, hemolysis and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mroQ mutant...
March 4, 2019: Infection and Immunity
Chance J Cosgriff, Chelsea R White, Wei Ping Teoh, James P Grayczyk, Francis Alonzo
Gram-positive bacteria process and release small peptides or "pheromones" that act as signals for the induction of adaptive traits including those involved in pathogenesis. One class of small signaling pheromones is the cyclic auto-inducing peptides (AIPs), which regulate expression of genes that orchestrate virulence and persistence in a range of microbes including Staphylococci, Listeria, Clostridia, and Enterococci. In a genetic screen for Staphylococcus aureus secreted virulence factors, we identified a S...
March 4, 2019: Infection and Immunity
Rudy Jacquet, Annette E LaBauve, Lavoisier Akoolo, Shivani Patel, Abdulelah A Alqarzaee, Tania Wong Fok Lung, Kunal Poorey, Timothy P Stinear, Vinai C Thomas, Robert Meagher, Dane Parker
Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus a major complication of diabetic wound infections. We investigated how the diabetic environment influences S. aureus skin infection and observed an increased susceptibility to infection in mouse models of both type I and type II diabetes. A dual gene expression approach was taken to investigate transcriptional alterations in both the host and bacterium after infection. While analysis of the host response revealed only minor changes between infected control and diabetic mice, we observed that S...
March 4, 2019: Infection and Immunity
Sukumar Pal, Delia F Tifrea, Luis M de la Maza
Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide and there is a need to control this epidemic. So far there is no established animal model in which both horizontal and vertical transmission of Chlamydia can be studied. To implement a horizontal sexual transmission model, male mice were inoculated in the meatus urethra with C. muridarum ( Cm ) and they were caged with naïve female mice. Urine and vaginal cultures were collected. To study vertical transmission newborns were euthanized and cultured...
March 4, 2019: Infection and Immunity
Alex J McCarthy, George M H Birchenough, Peter W Taylor
Gastrointestinal (GI) colonization of two-day-old (P2) rat pups with Escherichia coli K1 results in translocation of the colonizing bacteria across the small intestine, bacteremia and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection but not colonization is strongly age dependent: pups become progressively less susceptible to infection over the P2-P9 period. Colonization leads to strong down-regulation of the gene encoding trefoil factor 2 (Tff2), preventing maturation of the protective mucus barrier in the small intestine...
March 4, 2019: Infection and Immunity
Hernán F Peñaloza, Loreani P Noguera, Danielle Ahn, Omar P Vallejos, Raquel M Castellanos, Yaneisi Vazquez, Francisco J Salazar-Echegarai, Liliana González, Isidora Suazo, Catalina Pardo-Roa, Geraldyne A Salazar, Alice Prince, Susan M Bueno
Carbapenem-resistant Klebsiella pneumoniae ST258 (CRKP-ST258) can cause chronic infections in lungs and airways, with repeated episodes of bacteremia. In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin 10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of Monocyte-Myeloid Derived Suppressor Cells (M-MDSCs) and neutrophils that actively produce IL-10...
February 25, 2019: Infection and Immunity
Visnu Chaparro, Louis-Philippe Leroux, Aude Zimmermann, Armando Jardim, Brent Johnston, Albert Descoteaux, Maritza Jaramillo
CXCL16 is a multifunctional chemokine that is highly expressed by macrophages and other immune cells in response to bacterial and viral pathogens; however, little is known regarding the role of CXCL16 during parasitic infections. The protozoan parasite Leishmania donovani (L. donovani ) is the causative agent of visceral leishmaniasis. Even though chemokine production is a host defense mechanism during infection, subversion of the host chemokine system constitutes a survival strategy adopted by the parasite...
February 25, 2019: Infection and Immunity
Stephen T Smiley, Frank M Szaba, Lawrence W Kummer, Debra K Duso, Jr-Shiuan Lin
Plague is a rapidly lethal human disease caused by the bacterium Yersinia pestis (Yp). This study demonstrates that the Yp plasminogen activator Pla, a protease that promotes fibrin degradation, thwarts T cell-mediated defense against fully-virulent Yp. Introducing a single point mutation into the active site of Pla suffices to render fully-virulent Yp susceptible to primed T cells. Mechanistic studies reveal essential roles for fibrin during T cell-mediated defense against Pla-mutant Yp. Moreover, the efficacy of T cell-mediated protection against various Yp strains displays an inverse relationship with their levels of Pla activity...
February 25, 2019: Infection and Immunity
Aakanksha Gulati, Ranjai Kumar, Arunika Mukhopadhaya
Vibrio parahaemolyticus is a human pathogen, and it is a major cause of severe gastroenteritis in the coastal areas. OmpU is one of the major outer-membrane porins of V. parahaemolyticus Host-immunomodulatory effects of V. parahaemolyticus OmpU (VpOmpU) have not been elucidated yet. In this study towards characterizing the role of VpOmpU for its effect on innate immune responses of the host, we observed that VpOmpU gets recognized by TLR1/2 hetero-dimer in THP-1 monocyte but in RAW 264.7 macrophages VpOmpU gets recognized by both TLR1/2 and TLR2/6 hetero-dimers...
February 25, 2019: Infection and Immunity
Ricardo Mora-Cartiín, Cristina Gutieírrez-Jimeínez, Alejandro Alfaro-Alarcoín, Esteban Chaves-Olarte, Carlos Chacón-Díaz, Elías Barquero-Calvo, Edgardo Moreno
Brucella organisms are intracellular stealth pathogens of animals and humans. These bacteria overcome the assault of innate immunity at early stages of the infection. Removal of neutrophils (PMNs) at the onset of adaptive immunity against Brucella abortus , favored the bacterial elimination in mice. This was associated with higher levels of IFN-γ, and higher proportion of cells expressing IL-6 and iNOS, compatible with M1 macrophages, in the PMN-depleted B. abortus infected mice (PMNd- Br- mice). At later times of the acute infection phase, the amounts of IFN-γ lowered while the IL-6, IL-10 and IL-12 became the predominant cytokines in the PMNd- Br- mice...
February 25, 2019: Infection and Immunity
Helen E Rich, Collin C McCourt, Wen Quan Zheng, Kevin J McHugh, Keven M Robinson, Jieru Wang, John F Alcorn
Influenza kills 30-40,000 people each year in the United States, and causes ten times as many hospitalizations. A common complication of influenza is bacterial super-infection, which exacerbates morbidity and mortality from the viral illness. Recently, MRSA has emerged as the dominant pathogen found in bacterial super-infection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial super-infection. Current therapy for influenza/bacterial super-infection consists of treating the underlying influenza infection, adding various antibiotics which are increasingly rendered ineffective by rising bacterial multi-drug resistance...
February 25, 2019: Infection and Immunity
Leou Ismael Banla, Adam M Pickrum, Michael Hayward, Christopher J Kristich, Nita H Salzman
The human gastrointestinal tract (GIT) is inhabited by a dense microbial community of symbionts. Enterococci are one of the earliest members of this community and remain core members of the GIT microbiota throughout life. Enterococci have also recently emerged as opportunistic pathogens and major causes of nosocomial infections. Although recognized as a prerequisite for infection, colonization of the GIT by enterococci remains poorly understood. One way bacteria adapt to dynamic ecosystems like the GIT is through the use of their surface proteins to sense and interact with components of their immediate environment...
February 25, 2019: Infection and Immunity
Jacob E Choby, Andrew J Monteith, Lauren E Himmel, Paris Margaritis, Jana K Shirey-Rice, Andrea Pruijssers, Rebecca N Jerome, Jill Pulley, Eric P Skaar
Coagulation and inflammation are interconnected, suggesting coagulation plays a key role in the inflammatory response to pathogens. A Phenome-Wide Association Study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation Factor X. Patients with this SNP were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting Factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of Factor X deficiency...
February 19, 2019: Infection and Immunity
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