title: Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans.
abstract: The aim of this study was to assess the role of TLR2, TLR4 and MyD88 accessory molecule in the effector and secretory response of macrophages to viable microbial agents. Using TLR-deleted macrophage cell lines generated from the bone marrow of genetically engineered mice (TLR4 gene-deficient, MyD88- and TLR2-knockout mice) and wild-type control mice, we found that TLR2-deleted macrophages exhibit increased ability to contain Candida albicans infection compared to TLR2+/+ counterpart. In contrast, both MyD88-/- and TLR4-/- macrophages retain levels of functional activity comparable to that of the respective wild-type MyD88+/+ and TLR4+/+ controls. The difference in anticandidal effector functions observed between TLR2-/- and TLR2+/+ macrophages is abrogated upon opsonization of the fungal target and interestingly is not observed when using other microbial targets, such as Streptococcus pneumoniae and Helicobacter pylori. When tested for secretory response to C. albicans, TLR2-deleted macrophages show a pattern of cytokine production similar to that of TLR2+/+ controls. Finally, flow cytometry analysis reveals that TLR2-deleted macrophages express only TLR4, while, as expected, TLR2+/+ macrophages are both TLR2 and TLR4 positive; in no cases, modulation of such markers occurs in macrophages exposed to C. albicans infection. In conclusion, these data indicate that TLR2 and TLR4 have different biological relevance, in which TLR2 but not TLR4, is involved in the accomplishment of macrophage-mediated anticandidal activity, while the secretory response to C. albicans appears to be TLR4 but not TLR2-dependent.
authors.affiliation: Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy. blasi.elisabetta@unimore.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Blasi
authors.forename: Anna
authors.initials: A
authors.lastname: Mucci
authors.forename: Rachele
authors.initials: R
authors.lastname: Neglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzini
authors.forename: Bruna
authors.initials: B
authors.lastname: Colombari
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Volpini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Samuele
authors.initials: S
authors.lastname: Peppoloni
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D007113:Immunity, Innate; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D004247:DNA