Increased expression of IL-32 correlates with IFN-γ, Th1 and Tc1 in virologically suppressed HIV-1-infected patients.

Following recent attention focused on IL-32 as an important component involved in the inflammatory cytokine network, we speculated that IL-32's action on IFN-γ and IFN-γ secreting T cell subsets may help sustain the immune activation and dysregulation found in patients with HIV-1 achieving viral suppression. To explore this hypothesis, transcript levels of IL-32 and IFN-γ were evaluated in PBMC from 139 virologically suppressed HIV-1-infected patients and from 63 healthy individuals by Real Time RT-PCR assays. IL-32 and IFN-γ mRNA levels were also analyzed in CD4+ T cells, CD14+ monocytes and lamina propria lymphocytes (LPL) of the gut district in a subgroup of HIV-1-infected subjects. IFN-γ secreting CD4+ (Th1) and CD8+ (Tc1) T cell subset frequencies were evaluated in LPL by multiparametric flow cytometry. Gene expression results revealed that IL-32 and IFN-γ levels in PBMC from HIV-1-positive patients were significantly elevated compared to those from healthy donors, correlated with each other and increased with patient age. Both IL-32 and IFN-γ genes were also more strongly expressed in CD4+ T cells than in CD14+ monocytes. By contrast, IL-32 levels in LPL were comparable to those measured in PBMC, while IFN-γ levels were higher in PBMC than those in LPL. Negative correlations were found between IL-32 levels and the frequencies of Th1 and Tc1 subsets in gut mucosa. Collectively, our results provide the first evidence that IL-32 levels remain elevated in treated HIV-1-infected patients and correlate with IFN-γ, Th1 and Tc1 subsets.

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

Lack of association of Chlamydia pneumoniae with cardiovascular diseases in virologically suppressed HIV patients.

Cardiovascular disease (CVD) is a major public health problem in developed countries with over 17 million deaths per year. In the last decade, several infectious agents rather than any single pathogen, including Chlamydia pneumoniae and human immunodeficiency virus (HIV), have been shown to contribute to the development of atherosclerosis and subsequent cardiovascular events by inducing systemic inflammation and/or acting directly on the vascular wall. For the first time, we evaluated C. pneumonia DNA in peripheral blood mononuclear cells from HIV patients by real-time polymerase chain reaction in order to shed light on C. pneumonia as a co-factor with HIV in the development of CVDs. C. pneumonia DNA was not detected in our virologically suppressed HIV patients (<37 copies/mL). This finding may be related to high CD4+T cell count (>500 cells/µl) found in HIV patients suggesting functional cell-mediated immunity as a fundamental mechanism for the clearance of chlamydial infection in this population. Larger studies are needed to confirm this hypothesis.

Novel Insights and Features of the NDM-5-Producing Escherichia coli Sequence Type 167 High-Risk Clone.

Escherichia coli sequence type 167 (ST167), producing the metallo beta-lactamase NDM-5, has been isolated as a colonizer of patients recovered at the University Hospital Policlinico Umberto I of Rome. Phylogenesis and comparative analysis of the genomes of these strains were performed against 343 ST167 genomes available from the EnteroBase database. These analyses revealed that resistance plasmids, integrative conjugative elements (ICEs), carrying the yersiniabactin virulence trait and capsular synthesis gene clusters had variable compositions and distributions within different strains of the ST167 clone. A novel capsular synthesis gene cluster, highly similar to the K48 cluster previously described only for Klebsiella pneumoniae, was identified in phylogenetically related strains of the ST167 clone.IMPORTANCE Global dissemination of some E. coli high-risk clones has been described in the last decades. The most widespread was the ST131 clone, associated with extended-spectrum-beta-lactamase (ESBL) production. Genomics of ST131 demonstrated that one clade within the ST emerged in the early 2000s, followed by a rapid, global expansion. The E. coli ST167 clone is emerging throughout the world, being frequently reported for its association with carbapenem resistance. Our study shows that virulence features are differently represented within the ST167 population. One clade shows the K48 capsular synthesis gene cluster of K. pneumoniae, not previously described for E. coli, and is populated by NDM-5-producing strains. The combination of resistance and virulence may sustain the global expansion of this specific ST167 clade.

Yersinia enterocolitica in Italy: A Case of Septicemia and Abdominal Aortic Aneurysm Infection.

We report a case of Yersinia enterocolitica septicemia in a 63-year-old patient admitted to the Vascular Surgery Department of Umberto I Hospital (Rome, Italy) for an abdominal aortic aneurysm. The microorganism, recovered from both peripheral blood cultures and aneurysmatic aortic wall specimens, was identified as Y. enterocolitica using matrix-assisted laser desorption ionization-time of flight analysis (MALDI-TOF MS) and 16S rDNA gene sequencing. The isolate responsible for septicemia belonged to the O:9 serotype (biogroup 2). A genetic screening of the isolate made it possible to detect the presence of both the yst and ail genes, encoding a heat-stable enterotoxin and a protein involved in invasion/adherence and serum resistance, respectively. Our case contributes in enriching epidemiological data concerning Y. enterocolitica infections, which might represent severe complications in patients suffering from cardiovascular diseases. Moreover, this study, together with the others, should be regarded as valuable and useful tools for monitoring the rate of infections worldwide.

Cutaneous candidiasis caused by Candida albicans in a young non-immunosuppressed patient: an unusual presentation.

Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. There are over 20 species of Candida yeasts that can cause infection in humans, the most common of which is Candida albicans. Candida yeasts normally reside in the intestinal tract and can be found on mucous membranes and skin without causing infection. However, under immunocompromised conditions, Candida can cause significant infections in susceptible patients. Herein, we report a peculiar presentation of a C. albicans cutaneous infection in an immunocompetent young subject. This case widens our knowledge on the C. albicans infections both in terms of host susceptibility and cutaneous manifestations.

Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection.

In the cervicovaginal microenvironment, lactobacilli are known to protect against genital infections and, amongst the host defence compounds, lactoferrin has recently acquired importance for its anti-microbial and anti-inflammatory properties. An abnormal genital microenvironment facilitates the acquisition of pathogens like Chlamydia trachomatis, the leading cause of bacterial sexually transmitted infections worldwide. The aim of our study is to investigate the effects of Lactobacillus crispatus, Lactobacillus brevis and bovine lactoferrin on chlamydial infection, in order to shed light on the complex interplay between host defence mechanisms and C. trachomatis. We have also evaluated the effect of these defence factors to modulate the chlamydia-mediated inflammatory state. To this purpose, we have determined the infectivity and progeny production of C. trachomatis as well as interleukin-8 and interleukin-6 synthesis. The main result of our study is that the combination of L. brevis and bovine lactoferrin is the most effective in inhibiting the early phases (adhesion and invasion) of C. trachomatis infection of cervical epithelial cells and in decreasing the levels of both cytokines. In conclusion, the interaction between L. brevis and lactoferrin seems to play a role in the protection against C. trachomatis, reducing the infection and regulating the immunomodulatory activity, thus decreasing the risk of severe complications.