impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

More documents

Recommendations

Info

12 therefore of the Th1 development (Farrar 2002). Another transcription factor that is specific for Th2 cells is c-MAF, which is also responsible for regulating IL-4 synthesis through the activation of the IL-4 promoter ( Ho 1996). Once GATA-3 production reaches a certain threshold, its own gene expression is auto-activated, hence stabilizing the Th2 phenotype through an intrinsic positive-feedback loop (Farrar 2002). As Th2 cells mature, they produce increasing levels of IL-4, which generates a paracrine loop and induces neighboring naive T cells to develop into Th2 cells. IL-6, another cytokine released by macrophages, mast cells and pulmonary DCs during the early stages of a Th2 response, induces the Th2 phenotype through the up-regulation of IL-4 and inhibition of STAT1 phosphorylation, thereby preventing IFN-γ gene expression (Dodge 2003, Detournay 2005). In humans, IL-11 released by myeloid cells acts directly on T cells to stimulate IL-4 and IL-5 expression, while simultaneously inhibits IFN-γ production. IL-11 also suppresses IL-12 secretion and therefore also contributes to Th2 differentiation through this indirect mechanism ( Curti 2001). Activated DC2 may induce Th2 differentiation indirectly via the secretion of IL-10, which then inhibits IL-12 synthesis at mRNA level and thus the Th1 pathway (Koch 1996). IL-10 also down-regulates IL-12β2R expression (Romano 2005), suggesting that the development of the Th2 phenotype would be the default pathway, occurring spontaneously in the absence of IL- 12, but this is a point of controversy (Langenkamp 2000, Maldonado-López 2001). Whether DC2 secrete other soluble factors that promote Th2 cell development, remains unknown. Mast cell degranulation and mediator release can reduce the capacity of DCs to induce Th1 cells and promote the development of IL-4secreting T cells (Mazzoni 2006) suggesting that mast cells may have a role in the development of the antigenspecific Th2 cells in mast cell-related disorders, such as atopy. Several coreceptors are implicated in the activation and the reinforcement of the Th2 phenotype. Following Th cell activation, the costimulatory molecule ICOS is up-regulated and is retained on both effector and memory cells (Hutloff 1999). Its ligand (ICOS- L), is expressed on most APCs, including DCs, B cells, activated monocytes, fibroblasts and endothelial cells (Wassink 2004). ICOS participates in the regulation of T-cell activation by supporting the release of many cytokines (Okamoto 2004). ICOS –/– T cells are selectively deficient in IL-4 production (Nurieva 2005), and inhibition of ICOS activity results in the arrest of Th2 cell-mediated allergic airway responses without change of Th1-mediated IFN-γ secretion (Coyle 2000). Regulation of Th1/Th2 responses An impressive series of in vitro and in vivo data obtained in both experimental animals and humans, have shown that Th1 and Th2 responses are mutually regulated in a process known as re-direction or immune deviation. IL-12, IL-18, IFN-γ and IFN-α not only G. Del Prete - The complexity of the CD4 T-cell response favour the development of Th1 cells, but also inhibit the development of Th2 cells. Likewise, a number of pathogen products or even synthetic adjuvants, which are agonists of TLRs present on DCs and/or NK cells and are able to induce the production of IL-12 and/or IFNs by cells of the innate immunity, promote the shifting of Th2 responses to the less polarized Th0, or even to the Th1 polarized profile and effector functions (Erb 1998, Klinman 2004, Mohamadzadeh 2005, Revets 2005, Amedei 2006, Filì 2006). For example, the Neutrophil Activating Protein (HP-NAP) of Helicobacter pylori, a TLR2 agonist, is able to redirect to Th1 allergen-specific Th2 responses (Amedei 2006) (Figure 1). Even established human Th2 responses can be shifted, at least in vitro, to a Th1 profile by antigenstimulation in the presence of IL-12 (Annunziato 2001) and this phenomenon seems to be due to the IL- 12-induced long-term persistence of the β2 chain of the IL-12R, which is transiently expressed by Th2 cells after TCR stimulation alone (Smits 2001). Conversely, IL-4 inhibits Th1 cell development and shifts Th1 responses to a less-polarized phenotype, even if established Th1 responses seem to be less susceptible to redirection than Th2 responses (Ghoreschi 2003, Skapenko 2004). Fig. 1. Re-direction to Th1 of mite allergen-specific CD4 Th2 cells induced by H. pylori Neutrophil Activating Protein (HP- NAP). Mite allergen-induced T-cell lines were generated in the presence of medium alone, HP-NAP or IL-12. T-cell blasts of each line were then cloned and allergen-specific T cell clones were stimulated for 48 h with medium or the allergen in the presence of irradiated autologous APC. Culture supernatants were then collected and assayed for their IFN-γ and IL-4 content. Clones able to produce IFN-γ, but not IL-4, were categorized as Th1, clones producing IL-4 but not IFN-γ were coded as Th2, whereas clones producing both IFN-γ and IL-4 were categorized as Th0. Results represent mean percent proportions (+ SD) of clones with the indicated cytokine profile obtained from series of three T-cell lines for each condition.
Chemokines have several functions and exert chemotactic activity on several cell types, including Th1 and Th2 cells (Zlotnik 2000). The selective recruitment of Th1 cells at the site of tissue inflammation usually excludes Th2 cells and vice versa. However, some chemokines can influence also the polarization of Th1 or Th2 responses by directly interacting with these cells or their precursors and/or favouring the production of Th1- or Th2-promoting cytokines. It has been shown that IP-10/CXCL10 promotes the production of Th1and inhibits the production of Th2-cytokines, whereas PF-4/CXCL4 inhibits the production of Th1- and promotes the development of Th2-cytokines (Fliescher 2002; Romagnani 2005). While cytokines or chemokines can re-direct Th1/Th2 responses to a less polarized or even to the opposite phenotype, both types of effector cells are regulated by a heterogenous family of cells referred to as adaptive Tregs. Adaptive Tregs include: i) Th3 cells that are induced by oral antigen administration and exert their suppressive activity via the production of TGF-β (Weiner 2001), ii) T regulatory Tr1 cells, which are induced in the presence of IL-10 and exert their suppressive activity through IL-10 production (Roncarolo 2001), and (iii) a subset of CD4 + CD25 - cells that under certain condition can become CD4 + CD25 + and acquire the expression of Foxp3 (Chen 2003, Walker 2003). Neither Th3 nor Tr1 cells express Foxp3 and their suppressive effect is mediated by their TGF-β and IL-10 on both Th1 and Th2 responses through a MHC- and antigen-unrestricted mechanism (Vieira 2004). The functional mechanisms and even the origin of adaptive CD4 + CD25 + Foxp3 + cells are still unclear. TGF-β1 can convert CD4 + CD25 - T cells into Tregs in vitro (Chen 2003, Walker 2003, Fantini 2004, Zheng 2004). The Th17 lineage In recent years it has become evident that the diversity of CD4 effector T-cell responses has been underestimated. A lineage of IL-17-producing CD4 T helper (Th17) cells, which are distinct from Th1 and Th2 cells, was recently discovered and shown to be crucial Table 2. Induction and effects of CD4 Th17 cells G. Del Prete - The complexity of the CD4 T-cell response in autoimmune diseases and defence against extracellular bacteria (Murphy 2003, Nakae 2003, Harrington 2005, Langrish 2005, Park 2005). Th17 cells represent a distinct subset of effector T cells induced as a consequence of IL-23 production by DCs (Aggarwal 2003). IL-23 is a heterodimer that shares the p40 chain with IL-12, but differs in the presence of a p19 instead of the p35 chain. Similar subunits sharing occurs for the IL- 12R and the IL-23R: the IL-12R is a heterodimer composed of β1 and β2 chains, whereas the IL-23R contains the β1 chain but in combination with a specific receptor known as IL-23R (Kolls 2004). Th17 cells produce IL-17 or IL-17A and IL-17F, two of several members of the IL-17 family (Tato 2006), as well as IL- 22 (a member of the IL-10 family) (Liang 2006). These cytokines take part in inflammation by stimulating fibroblasts, endothelial cells, epithelial cells and macrophages to produce chemokines, as well as granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF, GM-CSF), with recruitment of polymorphonuclear leucocytes (Ye 2001) that may play an important role in the protection against extracellular bacteria (Cua 2003). In some conditions, however, IL- 17-induced inflammation is dominated by macrophages, with production of IL-1, IL-6, metalloproteinase (MMPP3) and inducible nitric oxide synthase (NOS2) (Park 2005) (Table 2). Th17 cells represent a distinct subset which does not express T-bet, GATA-3, or Foxp3 that are characteristic of Th1, Th2 and Treg cells, respectively, but the transcription factors involved in their development are still unknown (Dong 2006). Th17 cells are predominantly found in the lung and gut mucosa, suggesting a homeostatic role in these tissues ( Kryczek 2007). Both in vitro differentiation of Th17 cells and in vivo Th17-mediated inflammation are dependent on the transcription factor retinoic acid receptor-related orphan receptor γ-t (RORγt) (Ivanov 2006). The generation of Th17 cells is inhibited by IL-4 and IFN-γ, possibly via down-regulation of the IL-23R (Iwakura 2006). Furthermore, IL- 2, IL-25 and IL-27 play a role in abrogating Th17 cell development and in the suppression of inflammation in murine models of autoimmune disease; however, their Inducing elements Target cells Main effects Klebsiella pneumoniae, Bacterioides fragilis, Borrelia burgdorferi, Bordetella pertussis, Candida albicans Dendritic cells Production of IL-23, IL-6, TGF-β DCs + antigens + IL-23, IL-6, TGF-β Naïve T cell Differentiation into Th17 cells, production of IL-17A, IL-17F, IL-22, IL-6, TNF-α IL-17, IL-6, IL-22, TNF-α Endothelial cells, Fibroblasts, Epithelial cells, Macrophages Production of IL-1, IL-6, TNF-α, G-CSF, GM-CSF, MMPP3, NOS-2, CXCL1, CXCL2, CXCL5, CCL2, CCL5 Cytokines & chemokines Granulocytes, Macrophages Granulocyte recruitment, chronic inflammation, autoimmunity 13
Page 1 and 2: PARASSITOLOGIA A publication of the
Page 3: P A R A SSIT O L O GIA Founded in 1
Page 6 and 7: The individual authors take respons
Page 9: Parassitologia 50, 2008 RICORDO DEL
Page 13 and 14: Parassitologia 50: 9-16, 2008 The c
Page 15: eceptor subunits move closer togeth
Page 19 and 20: tion of the brain. Nature 421:744-8
Page 21 and 22: Parassitologia 50: 17-24, 2008 Epid
Page 23 and 24: adic or imported cases have been ob
Page 25 and 26: other EU countries, yet the impact
Page 27 and 28: Fasciola hepatica. II: La fasciolos
Page 29 and 30: Parassitologia 50: 25-29, 2008 Arte
Page 31 and 32: Ferry along the Potomac River. The
Page 33: for each of these chemical entities
Page 37: SIMPOSIO 1 ZOONOSI PROTOZOARIE: TOX
Page 40 and 41: 36 Many children with congenital to
Page 42 and 43: 38 Health promotion (Primary Preven
Page 44 and 45: 40 infants with CT newly synthesise
Page 46 and 47: 42 References Ades AE, Gilbert R, T
Page 49 and 50: Parassitologia 50: 45-50, 2008 Clin
Page 51 and 52: C. Contini - management of toxoplas
Page 53 and 54: C. Contini - management of toxoplas
Page 55 and 56: Parassitologia 50: 51-53, 2008 Toxo
Page 57: V. Meroni, F. Genco - Toxoplasmosis
Page 60 and 61: 56 A.W. Pfaff, E. Candolfi - Immuno
Page 62 and 63: 58 A.W. Pfaff, E. Candolfi - Immuno
Page 64 and 65: 60 (Kijlstra et al., 2006). Regardi
Page 67:
SIMPOSIO 2 IL PIANETA MALASSEZIA
Page 70 and 71:
66 C. Cafarchia, D. Otranto - Malas
Page 73 and 74:
Parassitologia 50: 69-71, 2008 Skin
Page 75:
E. M. Difonzo, E. Faggi - Skin dise
Page 78 and 79:
74 R. Galuppi, M.P. Tampieri - Mala
Page 80 and 81:
76 R. Galuppi, M.P. Tampieri - Mala
Page 82 and 83:
78 Table 1. Current composition of
Page 85 and 86:
Parassitologia 50: 81-83, 2008 Diag
Page 87:
tribution and population size of Ma
Page 90 and 91:
86 A. Peano, M.G. Gallo - Treatment
Page 92 and 93:
88 A. Peano, M.G. Gallo - Treatment
Page 94 and 95:
90 (vii) Antimycotic properties, pr
Page 97 and 98:
Parassitologia 50: 93-95, 2008 Unco
Page 99:
SIMPOSIO 3 AEDES ALBOPICTUS IN ITAL
Page 102 and 103:
98 test, whereas for the remaining
Page 104 and 105:
100 pyriproxyfen is twice as biolog
Page 107 and 108:
Parassitologia 50: 103-104, 2008 Bl
Page 109 and 110:
Parassitologia 50: 105-107, 2008 De
Page 111:
B. Cignini et al. - The ten-year ex
Page 114 and 115:
110 cumstances of isolation of Bahi
Page 117 and 118:
Parassitologia 50: 113-115, 2008 Im
Page 119:
for what concern the time of biting
Page 122 and 123:
118 during the past winter season w
Page 125 and 126:
Parassitologia 50: 121-123, 2008 Ae
Page 127:
fall recorded in the considered per
Page 130 and 131:
126 Remarks Surprisingly, except fo
Page 132 and 133:
128 Conclusion A. Tamburro - Admini
Page 135:
SIMPOSIO 4 IL RUOLO DELLA RICERCA N
Page 138 and 139:
134 approach and SAR studies. DDcl
Page 140 and 141:
136 Program financed by ANTIMAL. S.
Page 142 and 143:
138 A. della Torre et al. - Researc
Page 144 and 145:
140 A. della Torre et al. - Researc
Page 147 and 148:
Parassitologia 50: 143-145, 2008 He
Page 149:
E. Schwarzer et al. - Hemozoin and
Page 152 and 153:
148 geographic distribution in sub-
Page 154 and 155:
150 K.E., Beldjord, C., Nagel, R.L.
Page 157:
Parassitologia 50, 2008 Angelini P.
show all

impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

Create successful ePaper yourself

Delete template?

Save as template?