Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues. In addition to the local tissue microenvironment, both organ-specific dendritic cells and LN-resident stromal cells are critical factors to shape T cell migration properties. Here, we identify two additional homing-related molecules, CCR6 and Neuropilin-1 (Nrp1), upregulated in T cells early during differentiation solely in pLNs, but not mLNs. Surprisingly, intestinal inflammation resulted in an ameliorated induction of CCR6 and Nrp1 in pLNs, suggesting that a local inflammation within the gut can systemically alter T cell differentiation. Finally, transplantation of mLNs to a skin-draining environment revealed that LN stromal cells also contribute to efficient CCR6 induction in pLNs. Collectively, these findings identify further aspects of early T cell differentiation within skin-draining pLNs, which could be utilized to further develop tailored and highly specialized vaccination strategies.
Authors:Markus M. Heimesaat, Ursula Grundmann, Marie E. Alutis, André Fischer, Ulf B. Göbel, and Stefan Bereswill
Within 1 week following peroral Campylobacter jejuni infection, infant mice develop acute enteritis resolving thereafter. We here assessed colonic expression profiles of mediators belonging to the IL-23/IL-22/IL-18 axis and of matrix-degrading gelatinases MMP-2 and MMP-9 at day 6 post C. jejuni strain 81-176 infection. Whereas the pathogen readily colonized the intestines of infant IL-18−/− mice only, colonic mucin-2 mRNA, a pivotal mucus constituent, was downregulated in IL-22−/− mice and accompanied by increased expression of pro-inflammatory cytokines including IFN-γ, TNF, IL-17A, and IL-1β. Furthermore, in both naive and infected IL-22−/− mice, colonic expression of IL-23p19 and IL-18 was lower as compared to wildtype mice, whereas, conversely, colonic IL-22 mRNA levels were lower in IL-18−/− and colonic IL-18 expression lower in IL-23p19−/− as compared to wildtype mice. Moreover, colonic expression of MMP-2 and MMP-9 and their endogenous inhibitor TIMP-1 were lower in IL-22−/− as compared to wildtype mice at day 6 postinfection. In conclusion, mediators belonging of the IL-23/IL-22/IL-18 axis as well as the gelatinases MMP-2 and MMP-9 are involved in mediating campylobacteriosis of infant mice in a differentially regulated fashion.
Authors:Jennifer zur Bruegge, Christina Backes, Greta Gölz, Georg Hemmrich-Stanisak, Lydia Scharek-Tedin, Andre Franke, Thomas Alter, Ralf Einspanier, Andreas Keller, and Soroush Sharbati
The role of microRNAs (miRNAs) in infectious diseases is becoming more and more apparent, and the use of miRNAs as a diagnostic tool and their therapeutic application has become the major focus of investigation. The aim of this study was to identify miRNAs involved in the immune signaling of macrophages in response to Arcobacter (A.) butzleri infection, an emerging foodborne pathogen causing gastroenteritis. Therefore, primary human macrophages were isolated and infected, and miRNA expression was studied by means of RNAseq. Analysis of the data revealed the expression of several miRNAs, which were previously associated with bacterial infections such as miR-155, miR-125, and miR-212. They were shown to play a key role in Toll-like receptor signaling where they act as fine-tuners to establish a balanced immune response. In addition, miRNAs which have yet not been identified during bacterial infections such as miR-3613, miR-2116, miR-671, miR-30d, and miR-629 were differentially regulated in A. butzleri-infected cells. Targets of these miRNAs accumulated in pathways such as apoptosis and endocytosis — processes that might be involved in A. butzleri pathogenesis. Our study contributes new findings about the interaction of A. butzleri with human innate immune cells helping to understand underlying regulatory mechanisms in macrophages during infection.
Authors:Heike Granzer, Ralf Matthias Hagen, Philipp Warnke, Wolfgang Bock, Tobias Baumann, Norbert Georg Schwarz, Andreas Podbielski, Hagen Frickmann, and Thomas Koeller
This study addressed carbapenem-resistant Acinetobacter baumannii complex (ABC) isolates from patients that were injured during the military conflict in the Eastern Ukraine and treated at German Armed Forces Hospitals in 2014 and 2015. Clonal diversity of the strains and potential ways of transmission were analyzed.
Patients with one or several isolation events of carbapenem-resistant ABC were included. Isolates were characterized by VITEK II-based identification and resistance testing, molecular screening for frequent carbapenemase genes, and DiversiLab rep-PCRbased typing. Available clinical information of the patients was assessed.
From 21 young male Ukrainian patients with battle injuries, 32 carbapenem- and fluoroquinolone-resistant ABC strains were isolated. Four major clonal clusters were detected. From four patients (19%), ABC isolates from more than one clonal cluster were isolated. The composition of the clusters suggested transmission events prior to the admission to the German hospitals.
The infection and colonization pressure in the conflict regions of the Eastern Ukraine with ABC of low clonal diversity is considerable. Respective infection risks have to be considered in case of battle-related injuries in these regions. The low number of local clones makes any molecular exclusion of transmission events difficult.
Authors:Markus M. Heimesaat, Marie E. Alutis, Ursula Grundmann, André Fischer, Ulf B. Göbel, and Stefan Bereswill
We have recently shown that, within 1 week following peroral Campylobacter jejuni infection, conventional infant mice develop self-limiting enteritis. We here investigated the role of IL-23, IL-22, and IL-18 during C. jejuni strain 81-176 infection of infant mice. The pathogen efficiently colonized the intestines of IL-18−/− mice only, but did not translocate to extra-intestinal compartments. At day 13 postinfection (p.i.), IL-22−/− mice displayed lower colonic epithelial apoptotic cell numbers as compared to wildtype mice, whereas, conversely, colonic proliferating cells increased in infected IL-22−/− and IL-18−/− mice. At day 6 p.i., increases in neutrophils, T and B lymphocytes were less pronounced in gene-deficient mice, whereas regulatory T cell numbers were lower in IL-23p19−/− and IL-22−/− as compared to wildtype mice, which was accompanied by increased colonic IL-10 levels in the latter. Until then, colonic pro-inflammatory cytokines including TNF, IFN-γ, IL-6, and MCP-1 increased in IL-23p19−/− mice, whereas IL-18−/− mice exhibited decreased cytokine levels and lower colonic numbers of T and B cell as well as of neutrophils, macrophages, and monocytes as compared to wildtype controls. In conclusion, IL-23, IL-22, and IL-18 are differentially involved in mediating C. jejuni-induced immunopathology of conventional infant mice.
Authors:Cosme Alvarado-Esquivel, Luis Francisco Sánchez-Anguiano, Jesús Hernández-Tinoco, Rosa Angélica Pulido-Montoya, Guadalupe Acosta-Rojas, Sergio Estrada-Martínez, Alma Rosa Pérez-Álamos, Raquel Vaquera-Enriquez, Arturo Díaz-Herrera, Raúl Segura-Moreno, María de Lourdes Guerrero-Carbajal, Oliver Liesenfeld, Isabel Beristain García, and María Guadalupe Rentería-López
Medical certificates are documents that state the health status of a person. This study aimed to determine the seroprevalence and risk factors for Toxoplasma gondii infection in applicants of medical certificates and to investigate seroprevalence association with characteristics of these individuals. We examined 404 applicants in a public health center in Durango City, Mexico for the presence of anti-Toxoplasma IgG and IgM antibodies using enzyme-linked immunoassays. Of the 404 subjects (mean age of 35.94 ± 13.01) studied, 29 (7.2%) were positive for anti-T. gondii IgG antibodies and 9 (31.0%) of them were also positive for anti-T. gondii IgM antibodies. IgG and IgM seropositivities were associated with vision impairment (P = 0.04) and a history of surgery (P = 0.03), respectively. Prevalence of high (>150 IU/ml) IgG antibody levels was associated with hearing impairment (P = 0.03), and histories of lymphadenopathy (P = 0.04) and miscarriages (P = 0.03). Multivariate analysis showed that T. gondii seropositivity was associated with being born out of Durango State (odds ratio [OR] = 4.65; 95% confidence interval [CI]: 1.25– 17.29; P = 0.02) and soil contact (OR = 4.27; 95% CI: 1.71–10.67; P = 0.002) and negatively associated with consumption of sheep meat (OR = 0.12; 95% CI: 0.02–0.65; P = 0.01). These results could be used for the design of optimal preventive measures against toxoplasmosis and its sequelae.
Authors:Wycliffe Omurwa Masanta, Raimond Lugert, Uwe Groß, Gunter Linsel, Astrid Heutelbeck, and Andreas Erich Zautner
Several studies have shown that about 60–100% of farmed ducks are colonized by Campylobacter species. Because of this, a higher risk of campylobacteriosis among duck farm workers can be assumed.
To estimate the risk of Campylobacter infections in duck farm workers, we investigated the prevalence of Campylobacter spp. in ducks of two duck farms and the seroprevalence of anti-Campylobacter antibodies (IgA and IgG) in two cohorts of workers. The first cohort consisted of high-exposed stable workers and slaughterers, which was compared to a second cohort of non-/low-exposed persons. Duck caecal swabs and serum samples were collected in 2004, 2007, and 2010.
The colonization rate in the examined ducks was found to be 80–90%. The seroprevalence of anti-Campylobacter IgA and IgG antibodies among the non-exposed cohort was found to be 0.00% in all 3 years. In contrast, the exposed cohort demonstrated an IgA seroprevalence of 4.17% in 2004, 5.71% in 2007, and 0.00% in 2010 and an IgG seroprevalence of 8.33% in 2004, 0.00% in 2007, and 4.29% in 2010.
In conclusion, in 2004, we observed a significantly higher anti-Campylobacter antibody seroprevalence in the exposed cohort followed by a steady reduction in 2007 and 2010 under occupational health and safety measures.
Authors:Cosme Alvarado-Esquivel, Luis Francisco Sánchez-Anguiano, Jesús Hernández-Tinoco, Luis Omar Berumen-Segovia, Yazmin Elizabeth Torres-Prieto, Sergio Estrada-Martínez, Alma Rosa Pérez-Álamos, María Nalleli Ortiz-Jurado, Gabriel Molotla-de-León, Isabel Beristain-García, Elizabeth Rábago-Sánchez, and Oliver Liesenfeld
We assessed the association of Toxoplasma gondii infection and depression in a sample of psychiatric patients and control subjects without depression. We performed an age- and gender-matched case—control study of 89 patients suffering from depression attended in a public psychiatric hospital in Durango City, Mexico and 356 control subjects without depression from the general population of the same city. Participants were tested for the presence of anti-Toxoplasma IgG and IgM antibodies using enzymelinked immunoassays. Anti-T. gondii IgG antibodies were found in 11 (12.4%) of the 89 cases and in 22 (6.2%) of the 356 controls (OR = 2.14; 95% CI: 1.00–4.59; P = 0.04). Anti-T. gondii IgM antibodies were found in four (19%) of 21 anti-T. gondii IgG seropositive controls but not in 11 anti-T. gondii IgG seropositive cases (P = 0.27). Patients aged 30 years old and younger had a significantly higher seroprevalence of T. gondii infection than controls of the same age group (P = 0.001). Results of the present study suggest a potential association between T. gondii infection and depression. Furthers studies to confirm our results and to determine the epidemiology of T. gondii in young depressed patients should be conducted.
Emergence of extended-spectrum β-lactamase (ESBL) and fluoroquinolone resistance among ocular Enterobacteriaceae is increasing in higher frequency. Therefore, studies are being carried out to understand their multidrug resistance pattern. A total of 101 Enterobacteriaceae isolates recovered from various ocular diseases in a tertiary eye care center at Chennai, India during the period of January 2011 to June 2014 were studied. Forty one randomly chosen isolates were subjected to antibiotic susceptibility by minimum inhibitory concentration (MIC) and genotypic analysis. Of them, 16 were ESBL producers, one was carbapenemase producer and four were resistant to ertapenem which could be due to porin loss associated with AmpC production, and 17 were resistant to fluoroquinolones. Sixteen isolates harbored ESBL genes in which 14 had more than one gene and none of them were positive for blaNDM-1 gene. QNR genes were detected in 18 isolates.
ESBL producers were predominantly isolated from conjunctiva. A high degree of ESBL production and fluoroquinolone resistance is seen among the genus Klebsiella sp. Hence, monitoring the rate of ESBL prevalence plays a vital role in the administration of appropriate intravitreal antibiotics to save the vision and also to reduce the development of drug resistance in ocular pathogens.
Authors:Maria Franziska Ostermann, Heinrich Neubauer, Hagen Frickmann, and Ralf Matthias Hagen
This study assessed the variation of phenotypic features of clinical isolates of Burkholderia spp. from common rpsU gene sequence clusters.
A total of 41 clinical Burkholderia spp. isolates from German mucoviscidosis patients was subjected to rpsU gene sequencing. Biochemical assessment included the API systems 20 NE and 50 CHE as well as the Micronaut NF system. Fatty acid patterns were assessed using gas chromatography—mass spectrometry (GC—MS). Broth microdilution was used to identify minimum inhibitory concentrations.
Five rpsU gene sequence clusters comprised more than one clinical isolate. Altogether, assignments to three species and seven clusters comprising more than one Burkholderia species were performed. Inhomogeneity of biochemical reactions within the clusters ranged from 0/28 to 45/50 reactions. The standard deviation for fatty acid distributions ranged from 0% to 11.5%. Minimum inhibitory concentrations within the clusters showed a wide variation but only minor differences between the clusters.
Broad variations within identified rpsU gene sequence clusters regarding biochemical reactions, fatty acid patterns, and resistance patterns of clinical Burkholderia spp. isolates make the application of rpsU gene sequence analysis as a stand-alone procedure for discriminations within the Burkholderia cepacia complex unreliable.