CD5 on dendritic cells regulates CD4+ and CD8+ T cell activation and induction of immune responses.

The role of CD5 as a regulator of T cell signaling and tolerance is well recognized. Recent data show expression of CD5 on different subtypes of human dendritic cells, however its functional relevance in modulating DC mediated responses remains poorly understood. In this study, we show CD5 is expressed on CD11c+ DC from murine thymus, lymph node, spleen, skin and lung. Although the development of DC subpopulations in CD5-/- mice was normal, CD5-deficient DC produced significantly higher levels of IL-12 than wild type DC in response to LPS. CD5-/- DC, in comparison to CD5+/+ DC, enhanced the activation of CD4+ and CD8+ T cells in vitro and in vivo and induced significantly higher production of IL-2 and IFN-gamma by T cells. Consequently, CD5-/- DC were significantly more potent than wild type DC in the induction of anti-tumor immunity and contact hypersensitivity responses in mice. Restoration of CD5 expression in CD5-/- DC reduced IL-12 production and inhibited their capacity to stimulate T cells. Collectively, these data demonstrate that the specific expression of CD5 on DC inhibits the production of inflammatory cytokines and has a regulatory effect on their activity to stimulate T cells and induce immune responses. This study reveals a previously unrecognized regulatory role for CD5 on DC and provides novel insights into mechanisms for DC biology in immune responses.

Superoxide Production by NADPH Oxidase Intensifies Macrophage Antiviral Responses during Diabetogenic Coxsackievirus Infection.

Coxsackievirus B infections are suspected environmental triggers of type 1 diabetes (T1D) and macrophage antiviral responses may provide a link to virus-induced T1D. We previously demonstrated an important role for NADPH oxidase (NOX)-derived superoxide production during T1D pathogenesis, as NOX-deficient NOD mice (NOD.Ncf1m1J ) were protected against T1D due, in part, to impaired proinflammatory TLR signaling in NOD.Ncf1m1J macrophages. Therefore, we hypothesized that loss of NOX-derived superoxide would dampen diabetogenic antiviral macrophage responses and protect from virus-induced diabetes. Upon infection with a suspected diabetogenic virus, Coxsackievirus B3 (CB3), NOD.Ncf1m1J mice remained resistant to virus-induced autoimmune diabetes. A concomitant decrease in circulating inflammatory chemokines, blunted antiviral gene signature within the pancreas, and reduced proinflammatory M1 macrophage responses were observed. Importantly, exogenous superoxide addition to CB3-infected NOD.Ncf1m1J bone marrow-derived macrophages rescued the inflammatory antiviral M1 macrophage response, revealing reduction-oxidation-dependent mechanisms of signal transducer and activator of transcription 1 signaling and dsRNA viral sensors in macrophages. We report that superoxide production following CB3 infection may exacerbate pancreatic ß cell destruction in T1D by influencing proinflammatory M1 macrophage responses, and mechanistically linking oxidative stress, inflammation, and diabetogenic virus infections.

Regulation of early xenopus embryogenesis by Smad ubiquitination regulatory factor 2.

BACKGROUND: Smad ubiquitination regulatory factor (Smurf) 1 and 2 are E3 ubiquitin ligases originally identified as inhibitors of transforming growth factor beta signaling and are shown to modulate multiple cellular activities. The roles of Smurfs in vertebrate embryogenesis, however, are not completely understood. RESULTS: Here we investigate the function of Smurf2 during early Xenopus development. We show that distinctly from Smurf1, overexpression of Smurf2 in presumptive mesoderm interfered with mesoderm induction and caused axial defects, whereas knockdown of Smurf2 with antisense morpholino oligonucleotides resulted in expansion of the mesoderm. These results imply that Smurf2 may modulate nodal-mediated mesodermal induction. Consistently, ventral expression of Smurf2 induced a partial secondary axis with head structures. In the ectoderm, Smurf2 resembled Smurf1 in controlling neural and epidermal marker expression and influencing head formation. Smurf1, but not Smurf2, additionally affected neural tube closure. Interestingly, both Smurfs could enhance as well as repress neural crest markers, implying that they modulate their targets dynamically during neural plate border specification. CONCLUSION: Our data demonstrate that Smurf1 and Smurf2 have overlapping and distinct functionalities during early frog embryogenesis; collectively, they regulate ectodermal and mesodermal induction and patterning to ensure normal development of Xenopus embryos.

Outdoor airborne fungal spora load in a suburb of Kolkata, India: its variation, meteorological determinants and health impact.

Our objective was to conduct an aeromycological and health survey (2002-2007) in a suburban area near Kolkata, India, with the aim of achieving the following goals: (i) to prepare a fungal spore calendar, (ii) to determine the influence of different meteorological parameters, and (iii) to study the respiratory health status of local population in relation to allergy. Airborne fungal spores from more than 50 taxa were found, of which at least 15 were allergenic. The spore-concentration increased during early-winter and rainy season, and diminished during late-winter and mid-summer. Species-specific fluctuations had substantial influences from several meteorological parameters. The suburban area was found to be considerably contaminated with numerous allergenic air-spora, which caused health risk to the local population. Males were more susceptible to respiratory disorders irrespective of their age. In general, respiratory allergic patients in the 20-40 year age-group showed more frequent health problems due to aeroallergens. A positive correlation was found between the respiratory allergy cases and the air-spora concentrations.

Monitoring and assessment of airborne fungi in Kolkata, India, by viable and non-viable air sampling methods.

The composition and variability of airborne fungal spores were studied using two complementary sampling methods in an outdoor environment in Kolkata suburb for 2 years, from November 2002 to October 2004. For monitoring the total fungal spore burden in the air, Burkard 7-day volumetric sampler was used, whereas Andersen two-sage viable sampler was used for isolating the cultivable airborne fungi. Among the 37 fungal spore types identified in the air samples, the predominant ones were Cladosporium, unidentified ascospores, unidentified basidiospores, Aspergilli/Penicilli, Nigrospora, Periconia, Chaetomium, Drechslera, Alternaria, Coprinus, Ganoderma, Pithomyces, and rust spores. Only six fungal spore types (Alternaria, Aspergilli/Penicilli, Cladosporium, Curvularia, Drechslera, and Nigrospora) were recovered in common by the two samplers. For Aspergilli/Penicilli, Drechslera, and Nigrospora, the spore concentration was underestimated in the non-viable sampling method (Burkard sampler). In general, higher spore count was recorded in winter. The highest fungal species variability was observed in early monsoon (June). Relative humidity could significantly predict the seasonal periodicity of the maximum number of airborne spores. The total airborne fungi concentration recorded in the study (15-16 × 10(3) spores m(-3) of air) was lower than the proposed threshold limit value for clinical significance, suggesting apparently no or less airborne-fungi-exposure-related health risk in the sampling area. Cladosporium cladosporioides was recorded beyond the proposed threshold limit value in January 2003 and March 2004; Aspergillus fumigatus and Aspergillus nidulans in winter that might have posed considerable health risk to sensitized individuals.

Enumerating outdoor aeromycota in suburban West Bengal, India, with reference to respiratory allergy and meteorological factors.

Aeromycota may act as a reservoir of aeroallergens and upon inhalation may induce IgE-mediated Type I hypersensitivity reaction in pre-sensitized individuals. The total aerospora of an outdoor occupational setting (agricultural farm) in suburban West Bengal was sampled for two years (2002-2004) by a Burkard sampler. Concurrently, the cultivable aeromycota were trapped by an Andersen 2-stage sampler, cultured and tested for allergenic potential by skin prick test. The relationships between various climatic factors (temperature, relative humidity, rainfall and wind speed) and the distribution of aerospora were explored by Spearman correlation test. The antigenic extracts of 15 fungal species belonging to Alternaria, Aspergilli/Penicilli, Cladosporium, Curvularia, Drechslera, and Nigrospora evoked 10.8-54.8% skin reactivity in subjects with clinical history of respiratory allergy. The aerospora with skin sensitizing potential collectively represented a considerable fraction (52.3-58.4%) of the total aeromycota. The airborne concentration of Alternaria spores was higher than its borderline value of 100 spores m(-3) in May and June, whereas Cladosporium spore count exceeded its threshold limit value (3,000 spores m(-3)) in December, suggesting that this particular time of the year poses allergenic risk for individuals sensitive to these aerospora. Daily minimum temperature and rainfall appeared to be the most important meteorological factors to affect the concentration of aerospora in the study area.