scholarly journals Host Responses to the Pathogen Mycobacterium avium subsp. paratuberculosis and Beneficial Microbes Exhibit Host Sex Specificity

2014 ◽  
Vol 80 (15) ◽  
pp. 4481-4490 ◽  
Author(s):  
Enusha Karunasena ◽  
K. Wyatt McMahon ◽  
David Chang ◽  
Mindy M. Brashears
Keyword(s):  
Mycobacterium Avium ◽  
Sexual Transmission ◽  
Short Chain Fatty Acids ◽  
Host Responses ◽  
Host Immune System ◽  
Experimental Conditions ◽  
Male And Female ◽  
Content Type ◽  
Host Sex ◽  
Sex Specificity

ABSTRACTDifferences between microbial pathogenesis in male and female hosts are well characterized in disease conditions connected to sexual transmission. However, limited biological insight is available on variances attributed to sex specificity in host-microbe interactions, and it is most often a minimized variable outside these transmission events. In this work, we studied two gut microbes—a pathogen,Mycobacterium aviumsubsp.paratuberculosis, and a probiotic,Lactobacillus animalisNP-51—and the interaction between each agent and the male and female gastrointestinal systems. This trial was conducted in BALB/c mice (n= 5 per experimental group and per sex at a given time point), with analysis at four time points over 180 days. Host responses toM. aviumsubsp.paratuberculosisandL. animaliswere sensitive to sex. Cytokines that were significantly different (P≤ 0.05) between the sexes included interleukin-1α/β (IL-1α/β), IL-17, IL-6, IL-10, IL-12, and gamma interferon (IFN-γ) and were dependent on experimental conditions. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and IL-13/23 showed no sex specificity. A metabolomics study indicated a 0.5- to 2.0-fold (log2scale) increase in short-chain fatty acids (butyrate and acetate) in males and greater increases ino-phosphocholine or histidine from female colon tissues; variances distinct to each sex were observed with age or long-term probiotic consumption. Two genera,StaphylococcusandRoseburia, were consistently overrepresented in females compared to males; other species were specific to one sex but fluctuated depending on experimental conditions. The differences observed suggest that male and female gut tissues and microbiota respond to newly introduced microorganisms differently and that gut-associated microorganisms with host immune system responses and metabolic activity are supported by biology distinct to the host sex.

scholarly journals Bacterial Internalization, Localization, and Effectors Shape the Epithelial Immune Response during Shigella flexneri Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3624-3637 ◽  
Author(s):  
Juliane Lippmann ◽  
Frederik Gwinner ◽  
Camille Rey ◽  
Uyanga Tamir ◽  
Helen K. W. Law ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Shigella Flexneri ◽  
Host Responses ◽  
Host Immune System ◽  
Content Type ◽  
Infected Cells ◽  
Gene Expression Studies

Intracellular pathogens are differentially sensed by the compartmentalized host immune system. Nevertheless, gene expression studies of infected cells commonly average the immune responses, neglecting the precise pathogen localization. To overcome this limitation, we dissected the transcriptional immune response toShigella flexneriacross different infection stages in bulk and single cells. This identified six distinct transcriptional profiles characterizing the dynamic, multilayered host response in both bystander and infected cells. These profiles were regulated by external and internal danger signals, as well as whether bacteria were membrane bound or cytosolic. We found that bacterial internalization triggers a complex, effector-independent response in bystander cells, possibly to compensate for the undermined host gene expression in infected cells caused by bacterial effectors, particularly OspF. Single-cell analysis revealed an important bacterial strategy to subvert host responses in infected cells, demonstrating that OspF disrupts concomitant gene expression of proinflammatory, apoptosis, and stress pathways within cells. This study points to novel mechanisms through which bacterial internalization, localization, and injected effectors orchestrate immune response transcriptional signatures.

scholarly journals Host Responses to Persistent Mycobacterium avium SubspeciesparatuberculosisInfection in Surgically Isolated Bovine Ileal Segments

2012 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Chandrashekhar Charavaryamath ◽  
Patricia Gonzalez-Cano ◽  
Patrick Fries ◽  
Susantha Gomis ◽  
Kimberley Doig ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Lamina Propria ◽  
Mycobacterium Avium ◽  
Mesenteric Lymph Node ◽  
Cell Receptor ◽  
Host Responses ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Mesenteric Lymph

ABSTRACTA lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections withMycobacterium aviumsubsp.paratuberculosis. A model was developed for the controlled delivery of a defined dose ofM. aviumsubsp.paratuberculosisto surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistentM. aviumsubsp.paratuberculosisinfections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment.M. aviumsubsp.paratuberculosisremained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node.M. aviumsubsp.paratuberculosis-specific T cell proliferative responses included both CD4 and γδ T cell receptor (γδTcR) T cell responses in the draining mesenteric lymph node. The levels of CD8+and γδTcR+T cells increased significantly (P< 0.05) in the lamina propria, andM. aviumsubsp.paratuberculosis-specific tumor necrosis factor alpha (TNF-α) and gamma interferon secretion by lamina propria leukocytes was also significantly (P< 0.05) increased. There was a significant (P< 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed byM. aviumsubsp.paratuberculosisinfection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized entericM. aviumsubsp.paratuberculosisinfection in cattle and facilitated the analysis ofM. aviumsubsp.paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses toM. aviumsubsp.paratuberculosisinfection and improve vaccine strategies to preventM. aviumsubsp.paratuberculosisinfection.

scholarly journals Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

2013 ◽  
Vol 20 (12) ◽  
pp. 1817-1826 ◽  
Author(s):  
Ratna B. Gurung ◽  
Douglas J. Begg ◽  
Auriol C. Purdie ◽  
John P. Bannantine ◽  
Richard J. Whittington
Keyword(s):  
Mycobacterium Avium ◽  
Fusion Proteins ◽  
Physiological Stress ◽  
Binding Protein ◽  
Natural Infection ◽  
Factor Xa ◽  
Maltose Binding Protein ◽  
Host Immune System ◽  
Serum Samples ◽  
Content Type

ABSTRACTMycobacterium aviumsubsp.paratuberculosiscauses Johne's disease (JD) in ruminants. Proteomic studies have shown thatM. aviumsubsp.paratuberculosisexpresses certain proteins when exposed toin vitrophysiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be expressedin vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. aviumsubsp.paratuberculosisfusion proteins were evaluated using serum samples from sheep infected withM. aviumsubsp.paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced.

scholarly journals Infection with Mycobacterium avium subsp. paratuberculosis Results in Rapid Interleukin-1β Release and Macrophage Transepithelial Migration

2012 ◽  
Vol 80 (9) ◽  
pp. 3225-3235 ◽  
Author(s):  
Elise A. Lamont ◽  
Scott M. O'Grady ◽  
William C. Davis ◽  
Torsten Eckstein ◽  
Srinand Sreevatsan
Keyword(s):  
T Cells ◽  
Epithelial Cell ◽  
Mycobacterium Avium ◽  
Cross Talk ◽  
Interleukin 1Β ◽  
Host Responses ◽  
Acetoxymethyl Ester ◽  
Extracellular Medium ◽  
Content Type ◽  
Apical Side

ABSTRACTPathogen processing by the intestinal epithelium involves a dynamic innate immune response initiated by pathogen-epithelial cell cross talk. Interactions between epithelium andMycobacterium aviumsubsp.paratuberculosishave not been intensively studied, and it is currently unknown how the bacterium-epithelial cell cross talk contributes to the course of infection. We hypothesized thatM. aviumsubsp.paratuberculosisharnesses host responses to recruit macrophages to the site of infection to ensure its survival and dissemination. We investigated macrophage recruitment in response toM. aviumsubsp.paratuberculosisusing a MAC-T bovine macrophage coculture system. We show thatM. aviumsubsp.paratuberculosisinfection led to phagosome acidification within bovine epithelial (MAC-T) cells as early as 10 min, which resulted in upregulation of interleukin-1β (IL-1β) at transcript and protein levels. Within 10 min of infection, macrophages were recruited to the apical side of MAC-T cells. Inhibition of phagosome acidification or IL-1β abrogated this response, while MCP-1/CCL-2 blocking had no effect. IL-1β processing was dependent upon Ca2+uptake from the extracellular medium and intracellular Ca2+oscillations, as determined by EGTA and BAPTA-AM [1,2-bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester)] treatments. Thus,M. aviumsubsp.paratuberculosisis an opportunist that takes advantage of extracellular Ca2+-dependent phagosome acidification and IL-1β processing in order to efficiently transverse the epithelium and enter its niche—the macrophage.

THE PITUITARY AND ADRENAL RESPONSES TO ADMINISTRATION OF OESTRIOL IN GONADECTOMIZED RATS

1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Clinical Experience ◽  
Uterine Cervix ◽  
Morphological Changes ◽  
Physiological Significance ◽  
Female Rats ◽  
Experimental Conditions ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).

scholarly journals The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats

2021 ◽  
Vol 9 (5) ◽  
pp. 1037
Author(s):  
Craig Resch ◽  
Mihir Parikh ◽  
J. Alejandro Austria ◽  
Spencer D. Proctor ◽  
Thomas Netticadan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Female Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Ground Flaxseed ◽  
The Impact

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

scholarly journals Defects in Mitochondrial and Peroxisomal β-Oxidation Influence Virulence in the Maize Pathogen Ustilago maydis

2012 ◽  
Vol 11 (8) ◽  
pp. 1055-1066 ◽  
Author(s):  
Matthias Kretschmer ◽  
Jana Klose ◽  
James W. Kronstad
Keyword(s):  
Ustilago Maydis ◽  
Short Chain Fatty Acids ◽  
Phytopathogenic Fungi ◽  
Metabolic Adaptation ◽  
In Planta ◽  
Gene Encoding ◽  
Disease Symptoms ◽  
Content Type ◽  
C Terminus ◽  
Fungal Phytopathogens

ABSTRACTAn understanding of metabolic adaptation during the colonization of plants by phytopathogenic fungi is critical for developing strategies to protect crops. Lipids are abundant in plant tissues, and fungal phytopathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. Previously, we demonstrated a role for the peroxisomal β-oxidation enzyme Mfe2 in the filamentous growth, virulence, and sporulation of the maize pathogenUstilago maydis. However,mfe2mutants still caused disease symptoms, thus prompting a more detailed investigation of β-oxidation. We now demonstrate that a defect in thehad1gene encoding hydroxyacyl coenzyme A dehydrogenase for mitochondrial β-oxidation also influences virulence, although its paralog,had2, makes only a minor contribution. Additionally, we identified a gene encoding a polypeptide with similarity to the C terminus of Mfe2 and designated it Mfe2b; this gene makes a contribution to virulence only in the background of anmfe2Δ mutant. We also show that short-chain fatty acids induce cell death inU. maydisand that a block in β-oxidation leads to toxicity, likely because of the accumulation of toxic intermediates. Overall, this study reveals that β-oxidation has a complex influence on the formation of disease symptoms byU. maydisthat includes potential metabolic contributions to proliferationin plantaand an effect on virulence-related morphogenesis.

Behind closed doors! Homosocial desire and the academic boys club

2014 ◽  
Vol 29 (1) ◽  
pp. 44-64 ◽  
Author(s):  
Virginia Fisher ◽  
Sue Kinsey
Keyword(s):  
Design Methodology ◽  
Field Work ◽  
The Political ◽  
Detailed Data ◽  
Male And Female ◽  
Content Type ◽  
Feminist Poststructuralist ◽  
Homosocial Desire ◽  
Men And Masculinities ◽  
Practical Implications

Purpose – The aim of this paper is to explore the nature and power of the academic boys club. In many organisations, the political significance of the boys club goes largely unremarked and unacknowledged. Yet, the way that male colleagues intimately relate to each other, sometimes called homosocial desire, is crucial to their success at gaining and retaining power at work. Design/methodology/approach – Feminist, poststructuralist, ethnographic, qualitative, and longitudinal data were collected over a five-year period from male and female academics in a British university. Findings – The boys club is still a powerful feature of British universities. Their apparent invisibility shrouds the manner in which they can and do promote and maintain male interests in a myriad of ways, including selection and promotion. These findings have resonances for all organisations. Research limitations/implications – Researching the intimacies between male colleagues requires time-intensive field work and insider access to men interacting with each other. Practical implications – Meaningful gender equality will not be achieved unless and until the more sophisticated forms of female exclusion are revealed and deconstructed. Originality/value – This research makes an unusual and crucial contribution to the study of gender, men and masculinities by providing longitudinal, rich, detailed data, observing men at the closest of quarters and then analysed by a feminist and poststructuralist gaze.

scholarly journals Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

2016 ◽  
Vol 84 (8) ◽  
pp. 2198-2208 ◽  
Author(s):  
Colleen R. Eade ◽  
Chien-Che Hung ◽  
Brian Bullard ◽  
Geoffrey Gonzalez-Escobedo ◽  
John S. Gunn ◽  
...  
Keyword(s):  
Bile Acids ◽  
Type Iii Secretion ◽  
Acute Infection ◽  
Short Chain Fatty Acids ◽  
Common Mechanism ◽  
Environmental Cues ◽  
Anatomical Location ◽  
Content Type ◽  
Bacterial Signaling ◽  
The Individual

Salmonellaspp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded withinSalmonellapathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activatorhilDand to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant toSalmonellapathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressingSalmonellapathogenicity.

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