Publications by category
Journal articles
Salazar F, Brown GD (In Press). A friendly danger. Science, 362, 292-293.
Jiménez JM, Salazar M, Arancibia S, Villar J, Salazar F, Brown GD, Lavelle EC, Martínez-Pomares L, Ortiz-Quintero J, Lavandero S, et al (In Press). TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells from Mammals.
Frontiers in Immunology,
10Abstract:
TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells from Mammals
Mollusk hemocyanins have biomedical uses as carriers/adjuvants and nonspecific immunostimulants with beneficial clinical outcomes by triggering the production of proinflammatory cytokines in antigen-presenting cells (APCs) and driving immune responses toward type 1 T helper (Th1) polarization. Significant structural features of hemocyanins as a model antigen are their glycosylation patterns. Indeed, hemocyanins have a multivalent nature as highly mannosylated antigens. We have previously shown that hemocyanins are internalized by APCs through receptor-mediated endocytosis with proteins that contain C-type lectin domains, such as mannose receptor (MR). However, the contribution of other innate immune receptors to the proinflammatory signaling pathway triggered by hemocyanins is unknown. Thus, we studied the roles of Dectin-1, Dectin-2, and Toll-like receptor 4 (TLR4) in the hemocyanin activation of murine APCs, both in dendritic cells (DCs) and macrophages, using hemocyanins from Megathura crenulata (KLH), Concholepas concholepas (CCH) and Fissurella latimarginata (FLH). The results showed that these hemocyanins bound to chimeric Dectin-1 and Dectin-2 receptors in vitro; which significantly decreased when the glycoproteins were deglycosylated. However, hemocyanin-induced proinflammatory effects in APCs from Dectin-1 knock-out (KO) and Dectin-2 KO mice were independent of both receptors. Moreover, when wild-type APCs were cultured in the presence of hemocyanins, phosphorylation of Syk kinase was not detected. We further showed that KLH and FLH induced ERK1/2 phosphorylation, a key event involved in the TLR signaling pathway. We confirmed a glycan-dependent binding of hemocyanins to chimeric TLR4 in vitro. Moreover, DCs from mice deficient for MyD88-adapter-like (Mal), a downstream adapter molecule of TLR4, were partially activated by FLH, suggesting a role of the TLR pathway in hemocyanin recognition to activate APCs. The participation of TLR4 was confirmed through a decrease in IL-12p40 and IL-6 secretion induced by FLH when a TLR4 blocking antibody was used; a reduction was also observed in DCs from C3H/HeJ mice, a mouse strain with a nonfunctional mutation for this receptor. Moreover, IL-6 secretion induced by FLH was abolished in macrophages deficient for TLR4. Our data showed the involvement of TLR4 in the hemocyanin-mediated proinflammatory response in APCs, which could cooperate with MR in innate immune recognition of these glycoproteins.
Abstract.
Speakman EA, Dambuza IM, Salazar F, Brown GD (2020). T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Trends Immunol,
41(1), 61-76.
Abstract:
T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Fungi can cause disease in humans, from mucocutaneous to life-threatening systemic infections. Initiation of antifungal immunity involves fungal recognition by pattern recognition receptors such as C-type lectin receptors (CLRs). These germline-encoded receptors trigger a multitude of innate responses including phagocytosis, fungal killing, and antigen presentation which can also shape the development of adaptive immunity. Recently, studies have shed light on how CLRs directly or indirectly modulate lymphocyte function. Moreover, CLR-mediated recognition of commensal fungi maintains homeostasis and prevents invasion from opportunistic commensals. We present an overview of current knowledge of antifungal T cell immune responses, with emphasis on the role of C-type lectins, and discuss how these receptors modulate these responses at different levels.
Abstract.
Author URL.
Awuah D, Alobaid M, Latif A, Salazar F, Emes RD, Ghaemmaghami AM (2019). The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function. The Journal of Immunology, 203(1), 148-157.
Salazar F, Brown GD (2018). Antifungal innate immunity: a perspective from last 10 years.
Journal of Innate Immunity,
10, 373-397.
Abstract:
Antifungal innate immunity: a perspective from last 10 years
Fungal pathogens can rarely cause disease in immunocompetent individuals. However, commensal and normally non-pathogenic environmental fungi can cause life threatening infections in immunocompromised individuals. Over the last few decades, there has been a huge increase in the incidence of invasive opportunistic fungal infections along with a worrying increase in antifungal drug resistance. As a consequence, research focused on understanding the molecular and cellular basis of antifungal immunity has expanded tremendously in the last few years. This review will provide an overview of the most exciting recent advances in innate antifungal immunity, discoveries that are helping to pave the way for the development of new strategies that are desperately needed to combat these devastating diseases.
Abstract.
Riabov V, Salazar F, Htwe SS, Gudima A, Schmuttermaier C, Barthes J, Knopf-Marques H, Klüter H, Ghaemmaghami AM, Vrana NE, et al (2017). Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation. Acta Biomaterialia, 53, 389-398.
Salazar F, Awuah D, Negm OH, Shakib F, Ghaemmaghami AM (2017). The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs. Scientific Reports, 7(1).
Aldajani WA, Salazar F, Sewell HF, Knox A, Ghaemmaghami AM (2016). Expression and regulation of immune-modulatory enzyme indoleamine 2,3-dioxygenase (IDO) by human airway epithelial cells and its effect on T cell activation. Oncotarget, 7(36), 57606-57617.
Rostam HM, Singh S, Salazar F, Magennis P, Hook A, Singh T, Vrana NE, Alexander MR, Ghaemmaghami AM (2016). The impact of surface chemistry modification on macrophage polarisation. Immunobiology, 221(11), 1237-1246.
Salazar F, Hall L, Negm OH, Awuah D, Tighe PJ, Shakib F, Ghaemmaghami AM (2016). The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization. Journal of Allergy and Clinical Immunology, 137(6), 1841-1851.e2.
Ebensperger LA, León C, Ramírez-Estrada J, Abades S, Hayes LD, Nova E, Salazar F, Bhattacharjee J, Becker MI (2015). Immunocompetence of breeding females is sensitive to cortisol levels but not to communal rearing in the degu (Octodon degus). Physiology & Behavior, 140, 61-70.
Arancibia S, Espinoza C, Salazar F, Del Campo M, Tampe R, Zhong T-Y, De Ioannes P, Moltedo B, Ferreira J, Lavelle EC, et al (2014). A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma. PLoS ONE, 9(1), e87240-e87240.
Harrington H, Cato P, Salazar F, Wilkinson M, Knox A, Haycock JW, Rose F, Aylott JW, Ghaemmaghami AM (2014). Immunocompetent 3D Model of Human Upper Airway for Disease Modeling and in Vitro Drug Evaluation. Molecular Pharmaceutics, 11(7), 2082-2091.
Salazar F, Ghaemmaghami AM (2013). Allergen Recognition by Innate Immune Cells: Critical Role of Dendritic and Epithelial Cells. Frontiers in Immunology, 4
Salazar F, Sewell HF, Shakib F, Ghaemmaghami AM (2013). The role of lectins in allergic sensitization and allergic disease. Journal of Allergy and Clinical Immunology, 132(1), 27-36.
Arancibia S, Campo MD, Nova E, Salazar F, Becker MI (2012). Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects. European Journal of Immunology, 42(3), 688-699.
Manubens A, Salazar F, Haussmann D, Figueroa J, Del Campo M, Pinto JM, Huaquín L, Venegas A, Becker MI (2010). Concholepas hemocyanin biosynthesis takes place in the hepatopancreas, with hemocytes being involved in its metabolism. Cell and Tissue Research, 342(3), 423-435.
Publications by year
In Press
Salazar F, Brown GD (In Press). A friendly danger. Science, 362, 292-293.
Jiménez JM, Salazar M, Arancibia S, Villar J, Salazar F, Brown GD, Lavelle EC, Martínez-Pomares L, Ortiz-Quintero J, Lavandero S, et al (In Press). TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells from Mammals.
Frontiers in Immunology,
10Abstract:
TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells from Mammals
Mollusk hemocyanins have biomedical uses as carriers/adjuvants and nonspecific immunostimulants with beneficial clinical outcomes by triggering the production of proinflammatory cytokines in antigen-presenting cells (APCs) and driving immune responses toward type 1 T helper (Th1) polarization. Significant structural features of hemocyanins as a model antigen are their glycosylation patterns. Indeed, hemocyanins have a multivalent nature as highly mannosylated antigens. We have previously shown that hemocyanins are internalized by APCs through receptor-mediated endocytosis with proteins that contain C-type lectin domains, such as mannose receptor (MR). However, the contribution of other innate immune receptors to the proinflammatory signaling pathway triggered by hemocyanins is unknown. Thus, we studied the roles of Dectin-1, Dectin-2, and Toll-like receptor 4 (TLR4) in the hemocyanin activation of murine APCs, both in dendritic cells (DCs) and macrophages, using hemocyanins from Megathura crenulata (KLH), Concholepas concholepas (CCH) and Fissurella latimarginata (FLH). The results showed that these hemocyanins bound to chimeric Dectin-1 and Dectin-2 receptors in vitro; which significantly decreased when the glycoproteins were deglycosylated. However, hemocyanin-induced proinflammatory effects in APCs from Dectin-1 knock-out (KO) and Dectin-2 KO mice were independent of both receptors. Moreover, when wild-type APCs were cultured in the presence of hemocyanins, phosphorylation of Syk kinase was not detected. We further showed that KLH and FLH induced ERK1/2 phosphorylation, a key event involved in the TLR signaling pathway. We confirmed a glycan-dependent binding of hemocyanins to chimeric TLR4 in vitro. Moreover, DCs from mice deficient for MyD88-adapter-like (Mal), a downstream adapter molecule of TLR4, were partially activated by FLH, suggesting a role of the TLR pathway in hemocyanin recognition to activate APCs. The participation of TLR4 was confirmed through a decrease in IL-12p40 and IL-6 secretion induced by FLH when a TLR4 blocking antibody was used; a reduction was also observed in DCs from C3H/HeJ mice, a mouse strain with a nonfunctional mutation for this receptor. Moreover, IL-6 secretion induced by FLH was abolished in macrophages deficient for TLR4. Our data showed the involvement of TLR4 in the hemocyanin-mediated proinflammatory response in APCs, which could cooperate with MR in innate immune recognition of these glycoproteins.
Abstract.
2020
Speakman EA, Dambuza IM, Salazar F, Brown GD (2020). T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Trends Immunol,
41(1), 61-76.
Abstract:
T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors.
Fungi can cause disease in humans, from mucocutaneous to life-threatening systemic infections. Initiation of antifungal immunity involves fungal recognition by pattern recognition receptors such as C-type lectin receptors (CLRs). These germline-encoded receptors trigger a multitude of innate responses including phagocytosis, fungal killing, and antigen presentation which can also shape the development of adaptive immunity. Recently, studies have shed light on how CLRs directly or indirectly modulate lymphocyte function. Moreover, CLR-mediated recognition of commensal fungi maintains homeostasis and prevents invasion from opportunistic commensals. We present an overview of current knowledge of antifungal T cell immune responses, with emphasis on the role of C-type lectins, and discuss how these receptors modulate these responses at different levels.
Abstract.
Author URL.
2019
Awuah D, Alobaid M, Latif A, Salazar F, Emes RD, Ghaemmaghami AM (2019). The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function. The Journal of Immunology, 203(1), 148-157.
2018
Salazar F, Brown GD (2018). Antifungal innate immunity: a perspective from last 10 years.
Journal of Innate Immunity,
10, 373-397.
Abstract:
Antifungal innate immunity: a perspective from last 10 years
Fungal pathogens can rarely cause disease in immunocompetent individuals. However, commensal and normally non-pathogenic environmental fungi can cause life threatening infections in immunocompromised individuals. Over the last few decades, there has been a huge increase in the incidence of invasive opportunistic fungal infections along with a worrying increase in antifungal drug resistance. As a consequence, research focused on understanding the molecular and cellular basis of antifungal immunity has expanded tremendously in the last few years. This review will provide an overview of the most exciting recent advances in innate antifungal immunity, discoveries that are helping to pave the way for the development of new strategies that are desperately needed to combat these devastating diseases.
Abstract.
2017
Riabov V, Salazar F, Htwe SS, Gudima A, Schmuttermaier C, Barthes J, Knopf-Marques H, Klüter H, Ghaemmaghami AM, Vrana NE, et al (2017). Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation. Acta Biomaterialia, 53, 389-398.
Salazar F, Awuah D, Negm OH, Shakib F, Ghaemmaghami AM (2017). The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs. Scientific Reports, 7(1).
2016
Aldajani WA, Salazar F, Sewell HF, Knox A, Ghaemmaghami AM (2016). Expression and regulation of immune-modulatory enzyme indoleamine 2,3-dioxygenase (IDO) by human airway epithelial cells and its effect on T cell activation. Oncotarget, 7(36), 57606-57617.
Rostam HM, Singh S, Salazar F, Magennis P, Hook A, Singh T, Vrana NE, Alexander MR, Ghaemmaghami AM (2016). The impact of surface chemistry modification on macrophage polarisation. Immunobiology, 221(11), 1237-1246.
Salazar F, Hall L, Negm OH, Awuah D, Tighe PJ, Shakib F, Ghaemmaghami AM (2016). The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization. Journal of Allergy and Clinical Immunology, 137(6), 1841-1851.e2.
2015
Ebensperger LA, León C, Ramírez-Estrada J, Abades S, Hayes LD, Nova E, Salazar F, Bhattacharjee J, Becker MI (2015). Immunocompetence of breeding females is sensitive to cortisol levels but not to communal rearing in the degu (Octodon degus). Physiology & Behavior, 140, 61-70.
2014
Arancibia S, Espinoza C, Salazar F, Del Campo M, Tampe R, Zhong T-Y, De Ioannes P, Moltedo B, Ferreira J, Lavelle EC, et al (2014). A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma. PLoS ONE, 9(1), e87240-e87240.
Harrington H, Cato P, Salazar F, Wilkinson M, Knox A, Haycock JW, Rose F, Aylott JW, Ghaemmaghami AM (2014). Immunocompetent 3D Model of Human Upper Airway for Disease Modeling and in Vitro Drug Evaluation. Molecular Pharmaceutics, 11(7), 2082-2091.
2013
Salazar F, Ghaemmaghami AM (2013). Allergen Recognition by Innate Immune Cells: Critical Role of Dendritic and Epithelial Cells. Frontiers in Immunology, 4
Salazar F, Sewell HF, Shakib F, Ghaemmaghami AM (2013). The role of lectins in allergic sensitization and allergic disease. Journal of Allergy and Clinical Immunology, 132(1), 27-36.
2012
Arancibia S, Campo MD, Nova E, Salazar F, Becker MI (2012). Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects. European Journal of Immunology, 42(3), 688-699.
2010
Manubens A, Salazar F, Haussmann D, Figueroa J, Del Campo M, Pinto JM, Huaquín L, Venegas A, Becker MI (2010). Concholepas hemocyanin biosynthesis takes place in the hepatopancreas, with hemocytes being involved in its metabolism. Cell and Tissue Research, 342(3), 423-435.