Innate Immunity in the Clearance of Influenza A Virus Infected Apoptotic Cells

Summary

Principal Investigator: Kazue Takahashi
Abstract: [unreadable] Description (provided by applicant): Influenza infection is one of the leading causes of morbidity and mortality worldwide, with a commensurately large impact on healthcare spending. A striking feature of influenza A viral infection is the large number of apoptotic cells that result and which must be cleared in order to maintain homeostasis. The effector mechanisms of the innate immune system are critical to the recognition and removal of these apoptotic cells. The goal of this proposal is understanding how the innate immune system facilitates clearance of influenza A virus infection-induced apoptotic cells, and more generally how the innate immune system modulates the inflammatory response in the lungs. The focus of this proposal is mannose-binding lectin (MBL), a serum protein of the innate immune system that recognizes not only pathogens, including viruses, but also altered self, such as apoptotic cells. Our preliminary data indicate that (1) Lack of MBL impairs removal of apoptotic lymphocytes in lungs, the primary organ infected by infleunza A virus; (2) MBL binds to apoptotic lymphocytes; and (3) MBL plays a key role in the modulation of inflammation. Understanding the molecular aspects of the innate immunte system in clearing infection-induced aoptotic cells and regulating the inflammatory response during the removal of apoptotic cells will provide new therapeutic approaches to treat complications from virus infection and likely other chronic lung diseases. [unreadable] [unreadable] [unreadable]
Funding Period: 2007-09-25 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus
    Ian C Michelow
    From the Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
    J Biol Chem 285:24729-39. 2010
  2. pmc Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection
    Wei Chuan Chang
    Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    BMC Immunol 11:64. 2010
  3. pmc B cell subsets contribute to renal injury and renal protection after ischemia/reperfusion
    Brandon Renner
    Department of Medicine, University of Colorado Denver School of Medicine, Denver, CO 80045, USA
    J Immunol 185:4393-400. 2010
  4. pmc Complement 3 is involved with ventilator-induced lung injury
    Kazue Takahashi
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Int Immunopharmacol 11:2138-43. 2011
  5. pmc Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation
    Kazue Takahashi
    Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Immunobiology 216:96-102. 2011
  6. pmc High-dose mannose-binding lectin therapy for Ebola virus infection
    Ian C Michelow
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Infect Dis 203:175-9. 2011
  7. pmc Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin
    Wei Chuan Chang
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
    Biochem Pharmacol 81:388-95. 2011
  8. pmc The alternative pathway is required, but not alone sufficient, for retinal pathology in mouse laser-induced choroidal neovascularization
    Barbel Rohrer
    Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States
    Mol Immunol 48:e1-8. 2011

Detail Information

Publications8

  1. pmc A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus
    Ian C Michelow
    From the Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
    J Biol Chem 285:24729-39. 2010
    ..L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics...
  2. pmc Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection
    Wei Chuan Chang
    Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    BMC Immunol 11:64. 2010
    ..These clinical observations were confirmed by animal model studies, in which mice genetically lacking MBL were susceptible to certain pathogens, including herpes simplex virus 2...
  3. pmc B cell subsets contribute to renal injury and renal protection after ischemia/reperfusion
    Brandon Renner
    Department of Medicine, University of Colorado Denver School of Medicine, Denver, CO 80045, USA
    J Immunol 185:4393-400. 2010
    ..However, nonperitoneal B cells attenuate renal injury after I/R, possibly through the production of IL-10...
  4. pmc Complement 3 is involved with ventilator-induced lung injury
    Kazue Takahashi
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Int Immunopharmacol 11:2138-43. 2011
    ..We propose that C3 is involved with VILI and inhibition of complement activation may be a potential therapeutic strategy...
  5. pmc Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation
    Kazue Takahashi
    Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Immunobiology 216:96-102. 2011
    ..Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases...
  6. pmc High-dose mannose-binding lectin therapy for Ebola virus infection
    Ian C Michelow
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Infect Dis 203:175-9. 2011
    ..Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach...
  7. pmc Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin
    Wei Chuan Chang
    Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
    Biochem Pharmacol 81:388-95. 2011
    ..These results are encouraging that novel RCLs could be used as anti-IAV agents with less side effect and that RCLs would be suitable candidates in developing a new anti-IAV therapy...
  8. pmc The alternative pathway is required, but not alone sufficient, for retinal pathology in mouse laser-induced choroidal neovascularization
    Barbel Rohrer
    Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States
    Mol Immunol 48:e1-8. 2011
    ..Improving our understanding of the local regulation of this pathway in the eye is essential for developing improved treatment approaches for AMD...