Original Investigation

Medical Microbiology and Immunology

, Volume 203, Issue 4, pp 257-271

Open Access This content is freely available online to anyone, anywhere at any time.

Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin

  • Aline DupontAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Fatima MohamedAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Nur’Ain SalehenAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Sarah GlennAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Lorenza FrancescutAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Rozita AdibAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Simon ByrneAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Hannah BrewinAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
  • , Irina ElliottAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
    • , Luke RichardsAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
    • , Petya DimitrovaAffiliated withDepartment of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences
    • , Wilhelm SchwaebleAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
    • , Nina IvanovskaAffiliated withDepartment of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences
    • , Aras KadiogluAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
    • , Lee R. MachadoAffiliated withDepartment of Genetics, College of Medicine, Biological Sciences and Psychology, University of Leicester
    • , Peter W. AndrewAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester
    • , Cordula StoverAffiliated withDepartment of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester Email author 

Abstract

Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause severe infectious disease in human, were used to infect properdin-deficient and wildtype mice. The aim was to deduce a role for properdin, positive regulator of the alternative pathway of complement activation, by comparing and contrasting the immune response of the two genotypes in vivo. We show that properdin-deficient and wildtype mice mounted antipneumococcal serotype-specific IgM antibodies, which were protective. Properdin-deficient mice, however, had increased survival in the model of streptococcal pneumonia and sepsis. Low activity of the classical pathway of complement and modulation of FcγR2b expression appear to be pathogenically involved. In listeriosis, however, properdin-deficient mice had reduced survival and a dendritic cell population that was impaired in maturation and activity. In vitro analyses of splenocytes and bone marrow-derived myeloid cells support the view that the opposing outcomes of properdin-deficient and wildtype mice in these two infection models is likely to be due to a skewing of macrophage activity to an M2 phenotype in the properdin-deficient mice. The phenotypes observed thus appear to reflect the extent to which M2- or M1-polarised macrophages are involved in the immune responses to S. pneumoniae and L. monocytogenes. We conclude that properdin controls the strength of immune responses by affecting humoral as well as cellular phenotypes during acute bacterial infection and ensuing inflammation.

Keywords

Complement Mouse model Bacterial infection Dendritic cells Macrophages Fc receptor