Dupont, A., Mohamed, F., Salehen, N.'A., Glenn, S., Francescut, L., Adib, R., Byrne, S., Brewin, H., Elliott, I., Richards, L., Dimitrova, P., Schwaeble, W., Ivanovska, N., Kadioglu, A., Machado, L., Andrew, P. W. and Stover, C. (2014) Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin. Medical Microbiology and Immunology. 203(4), pp. 257-271. 0300-8584.
| Item Type: | Article |
|---|---|
| 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. |
| Additional Information: | A pre-publication version of this article was made available electronically by the publisher on 12 April 2014 |
| Uncontrolled Keywords: | Complement, mouse model, bacterial infection, dendritic cells, macrophages, Fc receptor |
| Subjects: |
Q Science > QR Microbiology > QR46 Medical microbiology R Medicine > RA Public aspects of medicine > RA421 Public health. Hygiene. Preventive Medicine |
| Creators: | Dupont, Aline, Mohamed, Fatima, Salehen, Nur'Ain, Glenn, Sarah, Francescut, Lorenza, Adib, Rozita, Byrne, Simon, Brewin, Hannah, Elliott, Irina, Richards, Luke, Dimitrova, Petya, Schwaeble, Wilhelm, Ivanovska, Nina, Kadioglu, Aras, Machado, Lee, Andrew, Peter W and Stover, Cordula |
| Publisher: | Springer |
| Northamptonshire and East Midlands: | Health |
| Faculties, Divisions and Institutes: |
University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Health Sciences and Services Research Centres > Centre for Physical Activity and Life Sciences |
| Date: | 1 August 2014 |
| Date Type: | Publication |
| Page Range: | pp. 257-271 |
| Journal or Publication Title: | Medical Microbiology and Immunology |
| Volume: | 203 |
| Number: | 4 |
| Language: | English |
| DOI: | https://doi.org/10.1007/s00430-013-0324-z |
| ISSN: | 0300-8584 |
| Status: | Published / Disseminated |
| URI: | http://nectar.northampton.ac.uk/id/eprint/6800 |
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