Abstract In humans, the type I interferon (IFN) family consists of 13 IFN‐α subtypes, IFN‐β and IFN‐o newly discovered IFN‐like IFN‐λ1, ‐λ2 ‐λ3. We have investigated expression λ IFN genes following virus infections or Toll‐like receptor (TLR) triggering in monocyte‐derived DC (MDDC) plasmacytoid (pDC). found thatall IFN‐α, ‐β, ‐o ‐λ subtypes are expressed influenza‐virus‐infected MDDC pDC. Conversely, differential gene transcription was induced pDC stimulated by specific TLR agonists. TLR‐9...

Abstract Macrophages and dendritic cells (DC) play an essential role in the initiation maintenance of immune response to pathogens. To analyze early interactions between Mycobacterium tuberculosis (Mtb) cells, human peripheral blood monocyte-derived macrophages (MDM) (MDDC) were infected with Mtb. Both found internalize mycobacteria, resulting activation MDM maturation MDDC as reflected by enhanced expression several surface Ags. After Mtb infection, proinflammatory cytokines TNF-α, IL-1,...

Emerging evidence points to an important role of autophagy in the immune response mediated by dendritic cells (DC) against Mycobacterium tuberculosis (Mtb). Since current vaccination based on Bacillus Calmette-Guerin (BCG) is unable stop epidemic, a deeper comprehension alterations induced Mtb DC essential for setting new vaccine strategies. Here, we compared capacity virulent (H37Rv) and avirulent (H37Ra) strains as well BCG modulate human primary DC. We found that H37Rv impairs at step...

Autophagy is a primordial eukaryotic pathway, which provides the immune system with multiple mechanisms for elimination of invading pathogens including Mycobacterium tuberculosis (Mtb). As consequence, Mtb has evolved different strategies to hijack autophagy process. Given crucial role human primary dendritic cells (DC) in host immunity control, we characterized Mtb-DC interplay by studying contribution cellular microRNAs (miRNAs) post-transcriptional regulation related genes. From...

As a result of their close association with the blood-brain barrier, astrocytes play an important role in regulating homing different leukocyte subsets to inflamed central nervous system (CNS). In this study, we investigated whether human produce chemokines that promote migration myeloid dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, show cultured stimulated interleukin-1β tumor necrosis factor CCL2, CCL3, CCL4, CCL5, CCL20,...

Abstract Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined presence and phenotype of plasmacytoid DCs (pDCs) synovial fluids (SF) patients with rheumatoid arthritis (RA), psoriatic (PA), osteoarthritis (OA) determined chemotactic properties SF from these toward pDCs. Flow cytometry analysis showed that percentage pDCs, identified as population Lin−CD123++ cells, is 4- 5-fold...

Abstract We recently reported that dendritic cells (DC) infected with Mycobacterium tuberculosis (Mtb) produce Th1/IFN-γ-inducing cytokines, IFN-αβ and IL-12. In the present article, we show maturing Mtb-infected DC express high levels of CCR7 they become responsive to its ligand CCL21. Conversely, CCR5 expression was rapidly lost from cell surface following Mtb infection. High CCL3 CCL4 were produced within 8 h after infection, which is likely account for observed down-modulation on DC....

Abstract Type I IFN regulates different aspects of the immune response, inducing a cell-mediated immunity. We have recently shown that infection dendritic cells (DC) with Mycobacterium tuberculosis (Mtb) induces IFN-α. In this work we monitored rapid induction IFN-β followed by delayed production IFN-α1 and/or -α13 subtypes. The Mtb rapidly activates NF-κB complex and stimulates phosphorylation regulatory factor (IRF)-3, events known to induce expression in viral infection. turn, autocrine...

The roles of plasmacytoid dendritic cells (pDCs) and their response to interferon (IFN)-β therapy in multiple sclerosis (MS) patients are poorly understood. We identified pDC accumulation white matter lesions leptomeninges MS brains abundant expression the Type I IFN-induced protein MxA, mainly perivascular CD3+ lymphocytes lesions, indicating IFN production by activated pDCs. chemoattractant chemerin was detected intralesional cerebrovascular endothelial cells, receptor expressed on...

Plasmacytoid DCs (pDCs) are crucial mediators in the establishment of immunity against most viruses, given their extraordinary capacity to produce a massive quantity type I IFN. In this study we investigate response pDCs infection with EBV, γ-herpes virus that persists an asymptomatic immunocompetent hosts, although certain conditions it can promote development cancers or autoimmune diseases. We show high amounts IFNs were released from isolated after exposure EBV by mechanism requiring TLRs...

Growing evidences put B lymphocytes on a central stage in multiple sclerosis (MS) immunopathology. While investigating the effects of interferon-β (IFN-β) therapy, one most used first-line disease-modifying drugs for treatment relapsing-remitting MS, circulating B-cell sub-populations, we found specific and marked decrease CD27+ memory cells. Interestingly, cells are considered population with great disease-driving relevance MS resulted to be also target depleting therapies. In addition,...

Abstract Macrophages have a central role in innate-immune responses to bacteria. In the present work, we show that infection of human macrophages with Gram-positive pathogenic Streptococcus pyogenes or nonpathogenic Lactobacillus rhamnosus GG enhances mRNA expression inflammatory chemokine ligands CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage-inflammatory protein-1α (MIP-1α), CCL5/regulated on activation, normal T expressed and secreted, CCL7/MCP-3, CCL19/MIP-3β,...

Type I IFN are cytokines which play a central role in host resistance to viral or microbial infections and important components linking innate adaptive immunity. We others have previously demonstrated that the production of IFN-beta by DC following bacterial TLR triggering influences, an autocrine manner, their maturation. In this study, we investigated whether release modulates phenotype immature response subsequent stimulation. The induction CD86, HLA-DR, CD38 B7H1 absence CCR7 CD83...

Aspergillus fumigatus is the most prevalent airborne fungal pathogen and causes fatal invasive aspergillosis in immunocompromised patients. Given essential role of dendritic cells (DC) initiating regulating immune responses, we investigated impact A. conidial infection on human DC. conidia were rapidly internalized induced release tumor necrosis factor alpha within first 8 h. After infection, majority DC underwent full maturation, although CCR7 expression was observed only that had conidia....

Abstract In human monocyte-derived dendritic cells (DC), infection with Mycobacterium tuberculosis and viruses or stimulation Toll-like receptor type 3 4 agonists causes the release of I interferon (IFN). Here, we describe that IFN-β released upon lipopolysaccharide (LPS) polyinosinic:polycytidylic acid (poly I:C) is responsible for a rapid sustained signal transducer activator transcription 1 2 activation expression IFN-stimulated genes, such as factor IFN regulatory 7 chemokine CXC ligand...

Abstract TLRs interact with a growing list of pathogen-derived products and these interactions drive the activation innate adaptive immune responses. Dendritic cells (DC) play key role in events expressing heterogeneous repertoire TLRs. We have previously demonstrated production type I IFNs DC following bacterial infections TLR triggering. In this study, we sought to characterize transcriptome specifically induced human by IFN-β stimulated upon LPS treatment. To aim, using cDNA microarrays,...

Abstract Given the variable protective efficacy provided by Mycobacterium bovis bacillus Calmette-Guérin (BCG), there is an urgent need to develop new vaccines against tuberculosis. As dendritic cells (DC) play a critical role in initiating and regulating T cell response pathogens, comprehension of mycobacterium-induced modulation DC functions pinpoint new, immunological strategies. To this end, comparative analysis effect induced BCG tuberculosis (Mtb) infection on immunophenotype indicated...

Background: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain cell abnormalities by directly targeting this lymphocyte population. Objectives: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of response relapsing–remitting (RRMS) having found low serum level Thymosin-α1 (Tα1) patients, we investigated whether the addition molecule peripheral blood mononuclear (PBMCs) would influence expansion...

The opportunistic pathogen Staphylococcus aureus (S. aureus) is a major cause of nosocomial- and community-acquired infections. In addition, many antibiotic-resistant strains are emerging worldwide, thus, there an urgent unmet need to pinpoint novel therapeutic prophylactic strategies. the present study, we characterized impact infection with pandemic methicillin-resistant USA300 S. strain on human primary dendritic cells (DC), key initiators regulators immune responses. particular, among...

Abstract The transcription factor STAT-4 plays a pivotal role in the IL-12-mediated development of naive CD4+ T cells into Th1 phenotype. Initially thought to be restricted lymphoid lineage, was subsequently shown expressed myeloid compartment, mainly activated monocytes, macrophages, and dendritic (DC). Here, we have studied human monocyte-derived DC, demonstrated that its expression can induced by multiple stimuli, such as ligands for TLR-4, TLR-2, TLR-3, different pathogens, CD40 ligand,...

Mycobacterium tuberculosis (Mtb) evades the immune response by impairing functions of different antigen‐presenting cells. We have recently shown that Mtb hijacks differentiation monocytes into dendritic cells (DCs). To further characterize mechanisms underlying this process, we investigated consequences inducing cell using interferon‐α and granulocyte‐macrophage colony‐stimulating factor in presence supernatants (SNs) obtained from monocyte cultures treated with or without heat‐inactivated...

The implication of B lymphocytes in the immunopathology multiple sclerosis (MS) is increasingly recognized. Here we investigated response cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored frequency TLR7-induced IgM and IgG-secreting patients levels found healthy donors, showing specific deficiency TLR7 pathway. However, no difference was observed TLR9 response. Furthermore, MS-derived PBMCs, TLR7-mediated production IL-6 ex...