title: Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin.
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.
authors.affiliation: Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester, University Road, Leicester, LE1 9HN, UK.
authors.forename: Aline
authors.initials: A
authors.lastname: Dupont
authors.forename: Fatima
authors.initials: F
authors.lastname: Mohamed
authors.forename: Nur'Ain
authors.initials: N
authors.lastname: Salehen
authors.forename: Sarah
authors.initials: S
authors.lastname: Glenn
authors.forename: Lorenza
authors.initials: L
authors.lastname: Francescut
authors.forename: Rozita
authors.initials: R
authors.lastname: Adib
authors.forename: Simon
authors.initials: S
authors.lastname: Byrne
authors.forename: Hannah
authors.initials: H
authors.lastname: Brewin
authors.forename: Irina
authors.initials: I
authors.lastname: Elliott
authors.forename: Luke
authors.initials: L
authors.lastname: Richards
authors.forename: Petya
authors.initials: P
authors.lastname: Dimitrova
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schwaeble
authors.forename: Nina
authors.initials: N
authors.lastname: Ivanovska
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: Lee R
authors.initials: LR
authors.lastname: Machado
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Cordula
authors.initials: C
authors.lastname: Stover
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008089:Listeria monocytogenes / Q000276:immunology*; D008810:Mice, Inbred C57BL; D011414:Properdin / Q000172:deficiency / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D011414:Properdin
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