An increase in the incidence of candidaemia and a predominance of Candida non-albicans due to decreasing use of fluconazole in favor of more potent antifungals, such as echinocandins, are reported in this study.

The immune response to pathogen is regulated by a combination of specific PRR, which are involved in pathogen recognition. Pseudomonas aeruginosa, a bacterium that causes life-threatening disease in immuno-compromised host, is recognized by distinct members of the TLR family. We have previously shown that viable P. aeruginosa bacteria are recognized by human monocytes mainly through TLR2. Using ligand-specific blocking antibodies, we herein show that the mannose receptor (MR), a phagocytic receptor for unopsonized P. aeruginosa bacteria, contributes equally to TLR2 in proinflammatory cytokine production by human monocytes in response to P. aeruginosa infection. Synergy of both receptors totally controls the immune response. Viable P. aeruginosa bacteria activate NF-jB and MAPK pathways and enhance TLR2-mediated signaling in MR-transfected human embryonic kidney 293 cells. Moreover, MR follows the same kinetics and colocalizes with TLR2 in the endosome during in vivo infection of human macrophages with P. aeruginosa. The studies provide the first demonstration of a significant role for MR, synergistic with TLR2, in activating a proinflammatory response to P. aeruginosa infection.Key words: Mannose receptor . NF-kB . Pseudomonas aeruginosa . TLR . TNF-a IntroductionThe innate immune system relies on a vast array of non-clonally expressed PRR to detect pathogens. PRR bind conserved molecular structures known as PAMP, which are shared by a large group of pathogens. PRR binding to microbial products elicits a signaling response within leukocytes to produce immune modulators in a PRR-dependent manner [1]. Proinflammatory cytokine production by monocyte/macrophage lineage orchestrates the immune response and predicts the outcome of infection. The overall immune response depends on the combination of engaged PRR and their specific ligands. This complexity allows the immune system not only to tailor its response to a specific pathogen but also to discriminate the site of infection or the microbial burden.Host recognition of PAMP may result in two entirely different outcomes. An appropriate response leads to the eradication of a microorganism [2], but an exaggerated inflammatory response may lead to illnesses such as sepsis and shock [3]. TLR are the best-characterized signal-generating receptors among the PRR. They initiate key inflammatory responses and shape adaptive immunity [4]. All human TLR ($11) are type I transmembrane glycoproteins containing an extracellular domain with leucinerich repeats responsible for ligand recognition and a cytoplasmic Toll/IL-1 receptor homology domain required for initiating signaling [5]. Working as homo-or heterodimers alone or with other PRR, they recognize a diverse array of microbial components in bacteria, fungi, parasites, and viruses. This includes lipid-based bacterial cell wall components such as LPS and lipopeptides, microbial protein components such as flagellin and profilin-like molecules, and nucleic acids such as dsRNA, ssRNA, and CpG DNA [6].TLR participate with additio...

TNF‐α production has a central role in the development and progression of Pseudomonas aeruginosa septic shock. We have previously shown that P. aeruginosa slime‐glycolipoprotein (slime‐GLP) is the most potent stimulant compared to P. aeruginosa lipopolysaccharide (LPS), for TNF‐α production and NF‐kB activation in human monocytes. Herein, we show that secretion of TNF‐α by fresh human monocytes, induced by P. aeruginosa slime‐GLP, LPS or viable bacteria, was paralleled by phosphorylation and/or activation of Mitogen‐activated Protein Kinases (MAPKs) ERK1/2, p38 as well as c‐Jun NH2‐terminal kinase. TNF‐α levels were significantly reduced by ERK1/2 inhibitor (PD98059), or p38 inhibitor (SB203580). Combination of both inhibitors almost abolished TNF‐α induction. Pseudomonas aeruginosa slime‐GLP differed from the P. aeruginosa‐LPS only regarding the strength of p38 and ERK1/2 activation, with slime‐GLP leading to a stronger activation of p38 and ERK1/2. Involvement of TLR2 and TLR4 for phosphorylation of p38 and ERK1/2 was shown using specific blocking anti‐TLR2 and anti‐TLR4 antibodies. Activation of both p38 and ERK1/2 induced by P. aeruginosa slime‐GLP was dramatically reduced in the presence of anti‐TLR2 and to a lesser degree in the presence of anti‐TLR4, whereas the P. aeruginosa‐LPS‐induced stimulation was inhibited only in the presence of anti‐TLR4. Our data show that P. aeruginosa viable bacteria, through slime‐GLP, stimulate specific members of the MAPKs more efficiently than the P. aeruginosa‐LPS, involving mainly TLR2.

BACKGROUNDBacillus subtilis (B. subtilis) is considered a non-pathogenic microorganism of the genus Bacillus and a common laboratory contaminant. Only scarce reports of B. subtilis central nervous system infection have been reported, mainly in the form of pyogenic meningitis, usually in cases of direct inoculation by trauma or iatrogenically.CASE SUMMARYA 51-year-old man, with a free previous medical history, presented to the Emergency Department of our hospital complaining of recurrent episodes of left upper limb weakness, during the last month, which had been worsened the last 48 h. During his presentation in Emergency Department he experienced a generalized tonic-clonic grand mal seizure. Brain magnetic resonance imaging (MRI) scan with intravenous Gadolinium revealed a 3.3 cm × 2.7 cm lesion at the right parietal lobe surrounded by mild vasogenic edema, which included the posterior central gyrus. The core of the lesion showed relatively homogenous restricted diffusion. Post Gadolinium T1W1 image, revealed a ring-shaped enhancement. Due to the imaging findings, brain abscess was our primary consideration. Detailed examination for clinical signs of infectious foci revealed only poor oral hygiene with severe tooth decay and periodontal disease, but without detection of dental abscess. The patient underwent surgical treatment with right parietal craniotomy and total excision of the lesion. Pus and capsule tissue grew B. subtilis and according to antibiogram intravenous ceftriaxone 2 g bids was administered for 4 wk. The patient remained asymptomatic and follow-up MRI scan two months after operation showed complete removal of the abscess.CONCLUSIONThis case highlights the ultimate importance of appropriate oral hygiene and dental care to avoid potentially serious infectious complications and second, B. subtilis should not be considered merely as laboratory contaminant especially when cultivated by appropriate central nervous system specimen.

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