Marina Botto

Factor I is required for the development of membranoproliferative glomerulonephritis in factor H-deficient mice (2008)

Rose, Kirsten L., Paixao-Cavalcante, Danielle, Fish, Jennifer, Manderson, Anthony P., Malik, Talat, Bygrave, Anne E., ...

The inflammatory kidney disease membranoproliferative glomerulonephritis type II (MPGN2) is associated with dysregulation. of the alternative pathway of complement activation. MPGN2 is characterized...

Serum Amyloid P Aids Complement-Mediated Immunity to Streptococcus pneumoniae (2007)

Jose Yuste, Marina Botto, Stephen E. Bottoms, Jeremy S. Brown

The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been...

Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains (2007)

Pickering, Matthew C., Goicoechea De Jorge, Elena, Martinez-Barricarte, Rubén, Recalde, Sergio, Garcia-Layana, Alfredo, Rose, Kirsten L., ...

We are grateful to all patients and the collaborating clinicians for their participation in this study. We thank Mr. Ian Shore for his technical assistance with the preparation of tissue for electron...

The in vivoexpression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus (2006)

Manderson, Anthony P, Carlucci, Francesco, Lachmann, Peter J, Lazarus, Robert A, Festenstein, Richard J, Cook, H Terence, ...

Abstract Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the...

The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus (2006)

Manderson, Anthony P., Carlucci,Francesco, Lachmann, J., Lazarus, Robert A ., Festenstein,Richard J, Cook, Terence, ...

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of...

Spontaneous Autoimmunity in 129 and C57BL/6 Mice—Implications for Autoimmunity Described in Gene-Targeted Mice (2004)

Anne E. Bygrave, Kirsten L. Rose, Josefina Cortes-Hernandez, Joanna Warren, Robert J. Rigby, H. Terence Cook, ...

Several strains of gene-targeted mice develop systemic lupus erythematosus (SLE). Analysis of these strains demonstrates that the genetic background profoundly influences the development of...

Spontaneous Autoimmunity in 129 and C57BL/6 Mice—Implications for Autoimmunity Described in Gene-Targeted Mice (2004)

Anne E. Bygrave, Kirsten L. Rose, Josefina Cortes-Hernandez, Joanna Warren, Robert J. Rigby, H. Terence Cook, ...

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop...

Phosphatidylserine receptor and apoptosis: consequences of a non-ingested meal (2004)

Botto, Marina

Abstract Apoptosis, a physiological process of controlled cell death, is essential during embryonic development and for the maintenance of tissue homeostasis. In recent years the view has emerged...

Links between complement deficiency and apoptosis (2001)

Botto, Marina

Abstract Deficiency in the classical pathway complement components displays a hierarchical association with the development of systemic lupus erythematosus (SLE). In addition, SLE causes consumption...

Complement Contributes to Protective Immunity against Reinfection by Plasmodium chabaudi chabaudi Parasites

Taylor, Philip R., Seixas, Elsa, Walport, Mark J., Langhorne, Jean, Botto, Marina

We have studied the impact of deficiency of the complement system on the progression and control of the erythrocyte stages of the malarial parasite Plasmodium chabaudi chabaudi. C1q-deficient mice...

Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis

Celik, Ilhan, Stover, Cordula, Botto, Marina, Thiel, Steffen, Tzima, Sotiria, Künkel, Dieter, ...

The complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading...

Increased Susceptibility of C1q-Deficient Mice to Salmonella enterica Serovar Typhimurium Infection

Warren, Joanna, Mastroeni, Pietro, Dougan, Gordon, Noursadeghi, Mahdad, Cohen, Jonathan, Walport, Mark J., ...

The role of the complement system in host defense against Salmonella infection is poorly defined. Bacterial cell wall O-antigen polysaccharide can activate the alternative pathway in vitro. No...

Links between complement deficiency and apoptosis

Botto, Marina

Deficiency in the classical pathway complement components displays a hierarchical association with the development of systemic lupus erythematosus (SLE). In addition, SLE causes consumption of...

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice

Brown, Jeremy S., Hussell, Tracy, Gilliland, Sarah M., Holden, David W., Paton, James C., Ehrenstein, Michael R., ...

The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by...

Phosphatidylserine receptor and apoptosis: consequences of a non-ingested meal

Botto, Marina

Apoptosis, a physiological process of controlled cell death, is essential during embryonic development and for the maintenance of tissue homeostasis. In recent years the view has emerged that dying...

Spontaneous Autoimmunity in 129 and C57BL/6 Mice—Implications for Autoimmunity Described in Gene-Targeted Mice

Bygrave, Anne E, Rose, Kirsten L, Cortes-Hernandez, Josefina, Warren, Joanna, Rigby, Robert J, Cook, H. Terence, ...

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop...

Loss of Complement Activation and Leukocyte Adherence as Nippostrongylus brasiliensis Develops within the Murine Host

Giacomin, Paul R., Wang, Hui, Gordon, David L., Botto, Marina, Dent, Lindsay A.

Complement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms....

The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus

Manderson, Anthony P, Carlucci, Francesco, Lachmann, Peter J, Lazarus, Robert A, Festenstein, Richard J, Cook, H Terence, ...

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of...

Complement Contributes to Protective Immunity against Reinfection by Plasmodium chabaudi chabaudi Parasites

Taylor, Philip R., Seixas, Elsa, Walport, Mark J., Langhorne, Jean, Botto, Marina

We have studied the impact of deficiency of the complement system on the progression and control of the erythrocyte stages of the malarial parasite Plasmodium chabaudi chabaudi. C1q-deficient mice...

Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis

Celik, Ilhan, Stover, Cordula, Botto, Marina, Thiel, Steffen, Tzima, Sotiria, Künkel, Dieter, ...

The complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading...

Increased Susceptibility of C1q-Deficient Mice to Salmonella enterica Serovar Typhimurium Infection

Warren, Joanna, Mastroeni, Pietro, Dougan, Gordon, Noursadeghi, Mahdad, Cohen, Jonathan, Walport, Mark J., ...

The role of the complement system in host defense against Salmonella infection is poorly defined. Bacterial cell wall O-antigen polysaccharide can activate the alternative pathway in vitro. No...

Links between complement deficiency and apoptosis

Botto, Marina

Deficiency in the classical pathway complement components displays a hierarchical association with the development of systemic lupus erythematosus (SLE). In addition, SLE causes consumption of...

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice

Brown, Jeremy S., Hussell, Tracy, Gilliland, Sarah M., Holden, David W., Paton, James C., Ehrenstein, Michael R., ...

The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by...

Phosphatidylserine receptor and apoptosis: consequences of a non-ingested meal

Botto, Marina

Apoptosis, a physiological process of controlled cell death, is essential during embryonic development and for the maintenance of tissue homeostasis. In recent years the view has emerged that dying...

Spontaneous Autoimmunity in 129 and C57BL/6 Mice—Implications for Autoimmunity Described in Gene-Targeted Mice

Bygrave, Anne E, Rose, Kirsten L, Cortes-Hernandez, Josefina, Warren, Joanna, Rigby, Robert J, Cook, H. Terence, ...

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop...

Loss of Complement Activation and Leukocyte Adherence as Nippostrongylus brasiliensis Develops within the Murine Host

Giacomin, Paul R., Wang, Hui, Gordon, David L., Botto, Marina, Dent, Lindsay A.

Complement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms....

The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus

Manderson, Anthony P, Carlucci, Francesco, Lachmann, Peter J, Lazarus, Robert A, Festenstein, Richard J, Cook, H Terence, ...

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of...

Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

Hutchinson, Winston L, Herbert, Jeff, Botto, Marina, Pepys, Mark B

During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the...

Monocytosis and accelerated activation of lymphocytes in C1q-deficient autoimmune-prone mice

Trendelenburg, Marten, Manderson, Anthony P, Fossati-Jimack, Liliane, Walport, Mark J, Botto, Marina

C1q deficiency has been shown to accelerate spontaneous autoimmunity in mice. We studied the time course of activation of monocytes and lymphocytes in autoimmune and non-autoimmune mice in the...

CD59a Deficiency Exacerbates Ischemia-Reperfusion Injury in Mice

Turnberg, Daniel, Botto, Marina, Lewis, Margarita, Zhou, Wuding, Sacks, Steven H., Morgan, B. Paul, ...

The terminal complement components C5a and the membrane attack complex are involved in the pathogenesis of ischemia-reperfusion injury in many organs. CD59 is the major regulator of membrane attack...

Borrelia burgdorferi Binding of Host Complement Regulator Factor H Is Not Required for Efficient Mammalian Infection▿

Woodman, Michael E., Cooley, Anne E., Miller, Jennifer C., Lazarus, John J., Tucker, Kathryn, Bykowski, Tomasz, ...

The causative agent of Lyme disease, Borrelia burgdorferi, is naturally resistant to its host's alternative pathway of complement-mediated killing. Several different borrelial outer surface proteins...

C1q deficiency promotes the production of transgenic-derived IgM and IgG3 autoantibodies in anti-DNA knock-in transgenic mice

Fossati-Jimack, Liliane, Cortes-Hernandez, Josefina, Norsworthy, Peter J., Walport, Mark J., Cook, H. Terence, Botto, Marina

C1q-deficient mice have been shown to develop a lupus-like disease and to display an impaired clearance of apoptotic cells that are enriched in lupus autoantigens. However, the role of C1q in the...

Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains

Pickering, Matthew C., De Jorge, Elena Goicoechea, Martinez-Barricarte, Rubén, Recalde, Sergio, Garcia-Layana, Alfredo, Rose, Kirsten L., ...

Factor H (FH) is an abundant serum glycoprotein that regulates the alternative pathway of complement-preventing uncontrolled plasma C3 activation and nonspecific damage to host tissues. Age-related...

Factor I is required for the development of membranoproliferative glomerulonephritis in factor H–deficient mice

Rose, Kirsten L., Paixao-Cavalcante, Danielle, Fish, Jennifer, Manderson, Anthony P., Malik, Talat H., Bygrave, Anne E., ...

The inflammatory kidney disease membranoproliferative glomerulonephritis type II (MPGN2) is associated with dysregulation of the alternative pathway of complement activation. MPGN2 is characterized...

Available carbon source influences the resistance of Neisseria meningitidis against complement

Exley, Rachel M., Shaw, Jonathan, Mowe, Eva, Sun, Yao-hui, West, Nicholas P., Williamson, Michael, ...

Neisseria meningitidis is an important cause of septicaemia and meningitis. To cause disease, the bacterium must acquire essential nutrients for replication in the systemic circulation, while...

C1q Governs Deposition of Circulating Immune Complexes and Leukocyte Fcγ Receptors Mediate Subsequent Neutrophil Recruitment

Stokol, Tracy, O'Donnell, Peter, Xiao, Ling, Knight, Sara, Stavrakis, George, Botto, Marina, ...

Inflammation induced by circulating immunoglobulin G–immune complexes (ICs) characterizes many immune-mediated diseases. In this work, the molecular requirements for the deposition of circulating...

Serum Amyloid P Aids Complement-Mediated Immunity to Streptococcus pneumoniae

Yuste, Jose, Botto, Marina, Bottoms, Stephen E, Brown, Jeremy S

The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been...

A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo

Taylor, Philip R., Carugati, Anna, Fadok, Valerie A., Cook, H. Terence, Andrews, Mark, Carroll, Michael C., ...

The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease...

Complement Activation Selectively Potentiates the Pathogenicity of the IgG2b and IgG3 Isotypes of a High Affinity Anti-Erythrocyte Autoantibody

Da Silveira, Samareh Azeredo, Kikuchi, Shuichi, Fossati-Jimack, Liliane, Moll, Thomas, Saito, Takashi, Verbeek, J. Sjef, ...

By generating four IgG isotype-switch variants of the high affinity 34–3C anti-erythrocyte autoantibody, and comparing them to the IgG variants of the low affinity 4C8 anti-erythrocyte autoantibody...

Continual Low-Level Activation of the Classical Complement Pathway

Manderson, Anthony P., Pickering, Matthew C., Botto, Marina, Walport, Mark J., Parish, Christopher R.

There is evidence that the classical complement pathway may be activated via a “C1-tickover” mechanism, analogous to the C3-tickover of the alternative pathway. We have quantitated and...

T Cell–dependent Immune Response in C1q-deficient Mice: Defective Interferon γ Production by Antigen-specific T Cells

Cutler, Antony J., Botto, Marina, Van Essen, Dominic, Rivi, Roberta, Davies, Kevin A., Gray, David, ...

The role of the classical complement pathway in humoral immune responses was investigated in gene-targeted C1q-deficient mice (C1qA−/−). Production of antigen-specific immunoglobulin (Ig)G2a and...

Impaired Opsonization with C3b and Phagocytosis of Streptococcus pneumoniae in Sera from Subjects with Defects in the Classical Complement Pathway▿

Yuste, Jose, Sen, Ashwin, Truedsson, Lennart, Jönsson, Göran, Tay, Liang-Seah, Hyams, Catherine, ...

Results from studies using mice deficient in specific complement factors and clinical data on patients with an inherited deficiency of the classical complement pathway component C2 suggest that the...

Factor H facilitates the clearance of GBM bound iC3b by controlling C3 activation in fluid phase

Paixão-Cavalcante, Danielle, Hanson, Steven, Botto, Marina, Cook, H. Terence, Pickering, Matthew C.

Dense deposit disease (DDD) is strongly associated with the uncontrolled activation of the complement alternative pathway. Factor H (CFH)-deficient (Cfh−/−) mice spontaneously develop C3...

CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche

Chevrier, Stéphane, Genton, Céline, Kallies, Axel, Karnowski, Alexander, Otten, Luc A., Malissen, Bernard, ...

Plasma cells represent the end stage of B-cell development and play a key role in providing an efficient antibody response, but they are also involved in numerous pathologies. Here we show that CD93,...