The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (DeltarodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.

The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fc␥ receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the devel- IntroductionNatural CD4 ϩ CD25 ϩ regulatory T cells (nTreg) expressing the lineage marker Foxp3 are the key players in controlling immune responses and in maintenance of T-cell homeostasis. 1,2 Therapeutic induction of the Treg represents a novel approach in the treatment of autoimmune pathology. 3,4 CD4 ϩ CD25 ϩ Foxp3 ϩ nTreg develop in thymus, in contrast to "adaptive" or "induced" Treg that develop in peripheral lymphoid tissues from CD4 ϩ conventional T cells (Tconv) and are frequently Foxp3 Ϫ . Although studies have highlighted the role of cytokines interleukin-2 (IL-2), transforming growth factor-␤ (TGF-␤), and IL-10 in Treg development, other factors or mechanisms crucial to Treg homeostasis are not elucidated. 5 Intravenous immunoglobulin (IVIg) is an established therapy for several immune disorders. [6][7][8][9] Several mutually nonexclusive mechanisms have been proposed to explain the beneficial effect of IVIg 7,8 ; however, the issue remains debated and an ongoing challenge. For instance, the Fc␥R-mediated effects of IVIg 10-12 cannot entirely account for its proven benefit in several peripheral and central demyelinating diseases such as GuillainBarré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and relapsing-remitting multiple sclerosis (MS), which are primarily mediated by autoreactive T cells. 6,7,13,14 Because the T cells do not express Fc␥R, 15 the observed effects raise certain speculations, that is, if these effects could be attributed to a direct interaction of the variable region of the immunoglobulin (Ig) G molecules with the T cell or an indirect influence via other cell types such as dendritic cells (DC).During the induction phase of experimental autoimmune encephalomyelitis (EAE), myelin reactive proinflammatory CD4 ϩ T cells proliferate in the periphery, infiltrate the central nervous system (CNS) during the effector phase and, in concert with other inflammatory mediators, lead to demyelination characterized by a progressive paralysis. 16 Natural remission and recovery from relapse in EAE is associated with the recruitment or generation of Treg in the CNS. 17,18 We and others have shown that IVIg protects against EAE development only when administered prophylactically. 14,19 We reasoned that IVIg manifests its protective effect in EAE through an early modulation of autoreactive T cells, and therefore we investigated the regulatory mechanisms, particularly the effect of IVIg on regulatory T cells. Methods Animals, antigen, and tissue culture mediumWe purchased C57BL/6J mice (females, 6-8 weeks of age) from Charles River Laboratories (L'Arbresle, F...

Initially used as a replacement therapy for immunodeficiency diseases, intravenous immunoglobulin (IVIg) is now widely used for a number of autoimmune and inflammatory diseases. Considerable progress has been made in understanding the mechanisms by which IVIg exerts immunomodulatory effects in autoimmune and inflammatory disorders. The mechanisms of action of IVIg are complex, involving modulation of expression and function of Fc receptors, interference with activation of complement and the cytokine network and of idiotype network, regulation of cell growth, and effects on the activation, differentiation, and effector functions of dendritic cells, and T and B cells.

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Background: Viscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression.

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International audienceIncreased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg