Authors:Greta Gölz, Gül Karadas, André Fischer, Ulf B. Göbel, Thomas Alter, Stefan Bereswill, and Markus M. Heimesaat
Arcobacter butzleri causes sporadic cases of gastroenteritis, but the underlying immunopathological mechanisms of infection are unknown. We have recently demonstrated that A. butzleri-infected gnotobiotic IL-10−/− mice were clinically unaffected but exhibited intestinal and systemic inflammatory immune responses. For the first time, we here investigated the role of Toll-like receptor (TLR)-4, the main receptor for lipopolysaccharide and lipooligosaccharide of Gram-negative bacteria, in murine arcobacteriosis. Gnotobiotic TLR-4/IL-10-double deficient (TLR-4−/− IL-10−/−) and IL-10−/− control mice generated by broad-spectrum antibiotics were perorally infected with A. butzleri. Until day 16 postinfection, mice of either genotype were stably colonized with the pathogen, but fecal bacterial loads were approximately 0.5–2.0 log lower in TLR-4−/− IL-10−/− as compared to IL-10−/− mice. A. butzleri-infected TLR-4−/− IL-10−/− mice displayed less pronounced colonic apoptosis accompanied by lower numbers of macrophages and monocytes, T lymphocytes, regulatory T-cells, and B lymphocytes within the colonic mucosa and lamina propria as compared to IL-10−/− mice. Furthermore, colonic concentrations of nitric oxide, TNF, IL-6, MCP-1, and, remarkably, IFN-γ and IL-12p70 serum levels were lower in A. butzleri-infected TLR-4−/− IL-10−/− versus IL-10−/− mice. In conclusion, TLR-4 is involved in mediating murine A. butzleri infection. Further studies are needed to investigate the molecular mechanisms underlying Arcobacter—host interactions in more detail.
Authors:Alex M. Nasaré, Roberto C. Tedesco, Priscila C. Cristovam, Marcos A. Cenedese, Andrés J. Galisteo Jr., Heitor F. Andrade Jr., José Álvaro P. Gomes, Érik V. Guimarães, Helene S. Barbosa, and Luis G. Alonso
HSP90B1 is a gene that codifies heat shock protein 108 (HSP108) that belongs to a group of proteins induced under stress situation, and it has close relation with the nervous system, especially in the retina. Toxoplasma gondii causes ocular toxoplasmosis that has been associated with a late manifestation of the congenital toxoplasmosis although experimental models show that morphological alterations are already present during embryological development. Here, we used 18 eyes of Gallus domesticus embryos in 7th and 20th embryonic days to establish a model of congenital ocular toxoplasmosis, experimentally infected in its fifth day correlating with HSP90B1 gene expression. Embryos’ eyes were histologically evaluated, and gene expression was performed by real-time polymerase chain reaction (PCR). Our data showed parasite present in the choroid, unusual migration of retinal pigment epithelium, and chorioretinal scars, and a tendency to a lower expression of the HSP90B1 gene upon experimental infection. This is a promising model to better understand T. gondii etiopathogeny.
Authors:Ralf Matthias Hagen, Hagen Hinz, and Hagen Frickmann
ESBL (extended-spectrum-β-lactamase)-positive Enterobacteriaceae, which colonized European soldiers in tropical Western African Mali, were subjected to a molecular assessment of their resistance determinants. By doing so, a better insight into the locally endemic pattern of ESBL-associated β-lactamase genes was aspired.
From a previous study on diarrhea in European soldiers on deployment in tropical Mali, 15 ESBL-positive Escherichia coli with demonstrated high clonal diversity and one positive Klebsiella pneumoniae were assessed. Polymerase chain reactions (PCRs) for blaTEM and blaSHV β-lactamase genes with subsequent sequencing for the discrimination of ESBL- and non-ESBL variants were performed, followed by four group-specific PCRs for blaCTX-M genes.
Non-ESBL-associated blaTEM-1 was identified in six out of 15 (40%) E. coli strains, while 100% of the assessed strains were positive for group I blaCTX-M.
Considering the known clonal diversity of the assessed strains, the striking restriction to one group of blaCTX-M genes accounting for the ESBL phenotypes of the isolates suggests little genetic exchange in the local setting. Under such circumstances of restricted numbers of locally endemic target genes, PCR-based screening approaches for ESBL colonization might be promising.
Hepatitis B and HIV infection are two viral infections that represent real global public health problems. In order to improve their management, some hypotheses suggest that genetic predispositions like ABO and Rh blood groups would influence the occurrence of these diseases.
The aim of the present study was to examine the association between ABO and Rhesus blood groups and the susceptibility to HIV infection and hepatitis B.
We conducted a cross-sectional and analytical study in a population of voluntary blood donors in the Blood Transfusion Center of Abidjan. All blood donors who donated blood between January and June 2014 were tested for HBs antigen and anti-HIV antibodies (ELISA tests) and were ABO typed.
The total number of examined blood donors during this period was 45,538, of which 0.32% and 8.07% were respectively infected with HIV and hepatitis B virus. O-group donors were more infected than non-O donors.
Our study is an outline concerning the search for a link between ABO and Rh blood groups and hepatitis B and HIV infection. Further studies should be conducted to confirm the interaction between these two infections and contribute to the search for new therapeutic approaches.
Authors:Markus M. Heimesaat, André Fischer, Anja A. Kühl, Ulf B. Göbel, Illana Gozes, and Stefan Bereswill
The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.
Authors:Klára Piukovics, Gabriella Terhes, Andrea Lázár, Flóra Tímár, Zita Borbényi, and Edit Urbán
From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment.
Authors:Marie E. Alutis, Ursula Grundmann, Ulrike Hagen, André Fischer, Anja A. Kühl, Ulf B. Göbel, Stefan Bereswill, and Markus M. Heimesaat
Increased levels of the matrix metalloproteinases (MMPs)-2 and -9 (also referred to gelatinase-A and -B, respectively) can be detected in the inflamed gut. We have recently shown that synthetic gelatinase blockage reduces colonic apoptosis and pro-inflammatory immune responses following murine Campylobacter (C.) jejuni infection. In order to dissect whether MMP-2 and/or MMP-9 is involved in mediating C. jejuni-induced immune responses, infant MMP-2-/-, MMP-9-/-, and wildtype (WT) mice were perorally infected with the C. jejuni strain B2 immediately after weaning. Whereas, at day 2 postinfection (p.i.), fecal C. jejuni B2 loads were comparable in mice of either genotype, mice expelled the pathogen from the intestinal tract until day 4 p.i. Six days p.i., colonic MMP-2 but not MMP-9 mRNA was upregulated in WT mice. Remarkably, infected MMP-2-/- mice exhibited less frequent abundance of blood in feces, less distinct colonic histopathology and apoptosis, lower numbers of effector as well as innate and adaptive immune cells within the colonic mucosa, and higher colonic IL-22 mRNA levels as compared to infected WT mice. In conclusion, these results point towards an important role of MMP-2 in mediating C. jejuni-induced intestinal immunopathogenesis.
Raw milk is a recognized source of Campylobacter outbreaks, but pasteurization is an effective way to eliminate the causative agent of Campylobacteriosis. Whereas breastfeeding is protective against infectious diseases, consumption of formula milk is thought to be not. However, in relation to Campylobacter, such data is currently unavailable. Although both pasteurized and formula milk are pathogen free and prepared in a quality controlled manner, the effect they have on the virulence of Campylobacter species is unknown. Here, we studied the effect of cow, goat, horse, and formula milk on Campylobacter invasion into intestinal epithelial Caco-2 cells, a pathogenic feature of this bacterial species, using a gentamicin exclusion invasion assay. We found that all milk products modulated the invasion of Campylobacter species into the Caco-2 cells in a dose-dependent manner. Control experiments showed that the milks were not toxic for the Caco-2 cells and that the effect on invasion is caused by heat labile (e.g., milk proteins) or heat stable (e.g., sugar/lipids) components depending on the Campylobacter species studied. This in vitro study shows for the first time that pasteurized and formula milk affect the invasion of Campylobacter. We recommend a prospective study to examine whether pasteurized and formula milk affect Campylobacteriosis.
Four species of Lejeunea viz., L. discreta, L. kashyapii, L. mehrana and L. parva are reported here for the first time from Meghalaya. Of which, Lejeunea kashyapii and L. mehrana are endemic, earlier reported from Sikkim only. The taxonomic description and illustrations of all are provided in present communication.
Authors:Ting Fu, Eva B. Znalesniak, Thomas Kalinski, Luisa Möhle, Aindrila Biswas, Franz Salm, Ildiko Rita Dunay, and Werner Hoffmann
The peptide trefoil factor family 3 (TFF3) is a major constituent of the intestinal mucus, playing an important role in the repair of epithelial surfaces. To further understand the role of TFF3 in the protection of intestinal epithelium, we tested the influence of TFF3 in a murine Toxoplasma gondii-induced ileitis model. Surprisingly, TFF3KO mice showed a reduced immune response in the ileum when compared to wild-type animals. Interleukin-12 and interferon-γ expression levels as well as the number of CD4+ lymphocytes were reduced in the infected TFF3KO mice. These effects were in line with the trend of elevated parasite levels in the ileum. Moreover, TFF1 expression was upregulated in the spleen of infected mice. These initial results indicate that TFF3 is involved in the immune pathology of T. gondii infection-induced intestinal inflammation. Thus far, the mechanisms of how TFF3 influences the immune response are not fully understood. Further studies should identify if TFF3 affects mucus sensing of dendritic cells and how TFF3 is involved in regulating the immune response as an intrinsic secretory peptide of immune cells.