New insights into pathogen recognition.

The Society for General Microbiology (SGM) Spring Conference covers a range of topics of microbiology and comprises mixed sessions including symposia, workshops, debates, offered papers and invited presentations from international experts. This year the SGM Conference was held 11-14 April 2011 at the Harrogate Conference Centre in Harrogate, Yorkshire (UK). The main aim of the meeting is generally to provide a variety of programs that reflect current knowledge on different topics and introduce the recent advances in general and applied microbiology. Aspects of microbial recognition and interaction with the host immune response were addressed during a session of the meeting, where leaders in the field highlighted how the immune system is designed to recognize and destroy microorganisms by detecting microbial signature molecules (pathogen-associated molecular patterns) via interaction with specific receptors. This article focuses on the current research on pathogen recognition by the host through the interaction with surface structures present on microorganisms, with particular interest on the family of lectins, an emerging area in the understanding of infectious diseases. Discovering the mechanisms used by bacteria to survive in the host environment and at the same time elucidating the processes by which the immune system interacts with pathogens is vital for the development of vaccines and the design of new therapies

FORMATION AND STRUCTURE OF TIN-IRON OXIDE THIN-FILM CO SENSORS

Rheotaxial growth and thermal oxidation (RGTO) for depositing thin films is a recognized technique in preparing gas sensitive semiconducting oxides. This paper presents a study performed by x-ray diffraction and scanning Auger microscopy of the mechanisms of growth and formation of the thin films of the new ternary compound Sn1-xFexOy with an iron content in the range 0 < x < 25 at. %. A structural model of this compound, which is found to be stable over a very large range of Sn/Fe ratios, can be derived by partially substituting Fe3+ ions in Sn4+ sites. This is an easy substitution in view of the similar values shown by the ionic radii (Fe3+ = 0.64 angstrom, Sn4+ = 0.71 angstrom) and the Pauling electronegativity (Fe3+ = 1.8, Sn4+ = 1.8) of these two ions. Experimental data, showing that this material is an excellent CO sensor, are reported

Serum and urinary levels of IL-18 and its inhibitor IL-18BP in systemic lupus erythematosus.

Overproduction of inflammation-related cytokines plays an important role in systemic lupus erythematosus (SLE). A crucial cytokine is IL-18, a member of the IL-1 family involved in the regulation of both innate and acquired immune responses. The aim of this study was to evaluate free IL-18 levels in the serum and urine of SLE patients, in order to establish their relationship with other biomarkers of disease activity. Serum and urine levels of IL-18 and IL-18BP were measured by ELISA in 50 SLE patients and in 32 healthy subjects; free IL-18 was calculated using the law of mass action. Serum levels of total IL-18, IL-18BP and free IL-18 were higher in SLE patients than in healthy controls. Total and free serum IL-18 levels were higher in patients with active disease (with nephritis or active non-renal disease), and correlated with the ECLAM score. Urinary levels of total and free IL-18 were higher in patients than in controls, but did not correlate with disease activity. The data collected in this study show that increased levels of both IL-18 and its natural inhibitor IL-18BP, characterise SLE. Despite the overproduction of IL-18BP, free IL-18 is still significantly higher in SLE patients than in controls, and its serum levels are a marker of disease activity

IL-18 in autoimmunity. Studies in autoimmune murine lupus and in human SLE

The chronic progressive lupus-like disease of lpr mice strongly involves Th1-dependent immune activation. Expression of the Th1-related cytokine IL-18 and of its receptors is greatly enhanced in lpr lymphoid organs early in life, well before pathology development. Hyper-expression of the Th2-activating IL-18-like cytokine IL-33 was evident in lpr mice, in parallel to increase of receptor expression. Expression of IL-17, present in normal organs, was undetectable in lpr mice. Thus, autoimmune pathogenesis in murine lupus correlates with up-regulation of Th1 and Th2 responses, with no involvement of Th17 reactions. In human lupus patients, serum and urine levels of IL-18 and its inhibitor IL-18BP were higher than in controls. However, only serum levels of IL-18BP positively correlated with disease severity (ECLAM score)

Galectin-3 binds Neisseria meningitidis and increases interaction with phagocytic cells.

Galectin-3 is expressed and secreted by immune cells and has been implicated in multiple aspects of the inflammatory response. It is a glycan binding protein which can exert its functions within cells or exogenously by binding cell surface ligands, acting as a molecular bridge or activating signalling pathways. In addition, this lectin has been shown to bind to microorganisms. In this study we investigated the interaction between galectin-3 and Neisseria meningitidis, an important extracellular human pathogen, which is a leading cause of septicaemia and meningitis. Immunohistochemical analysis indicated that galectin-3 is expressed during meningococcal disease and colocalizes with bacterial colonies in infected tissues from patients. We show that galectin-3 binds to N. meningitidis and we demonstrate that this interaction requiresfull-length, intact lipopolysaccharide molecules. We found that neither exogenous nor endogenous galectin-3 contributes to phagocytosis of N. meningitidis; instead exogenous galectin-3 increases adhesion to monocytes and macrophages but not epithelial cells. Finally we used galectin-3 deficient (Gal-3(-/-) ) mice to evaluate the contribution of galectin-3 to meningococcal bacteraemia. We found that Gal-3(-/-) mice had significantly lower levels of bacteraemia compared with wild-type mice after challenge with live bacteria, indicating that galectin-3 confers an advantage to N. meningitidis during systemic infection

IL-18 activity in systemic lupus erythematosus

Interleukin-18 (IL-18) is an inflammation-related cytokine that plays a central role both in innate defense reactions and in Th1 activation and specific immune responses. Increased levels of IL-18 can be detected in biological fluids and organs of individuals affected by several autoimmune pathologies, as well as in autoimmune animal models. In this review, the role of IL-18 in systemic lupus erythematosus (SLE) is critically examined, including its possible role in the pathogenesis of disease. In SLE, increased levels of IL-18 have been found in serum/plasma of affected persons, which positively correlated with disease severity. The possibility that circulating IL-18 levels are predictive of renal damage has been proposed, suggesting that IL-18 may be a prognostic marker of renal involvement useful to identify patients at risk of renal failure. The evaluation of urinary levels of free active IL-18 indeed suggests a correlation with the degree of renal involvement. The possible pathogenic role of IL-18 in lupus has been studied in a mouse model of progressive disease, which makes possible the identification, at the level of the different affected organs, of IL-18 changes preceding disease development and those appearing after disease onset. It can be concluded that IL-18 has a multifaceted role in autoimmune lupus, being apparently involved both in the effector phases of the late organ damage and, in some organs, in the initial pathogenic events. Therapeutic strategies targeting IL-18 in autoimmunity are under development