Bacterial evasion of innate immunity
Principal investigator; Areschoug, Thomas, , PhD
Co-workers, not Lund University: Lambeau Gerard, Martinez Fernando, Nizet Victor, Ramsland Paul, Touqui Lhousseine, Varki Ajit
Antigen-presenting cells, such as macrophages, are widely distributed in the human body, including at sites of possible entry for pathogenic microorganisms. Macrophages express several surface molecules collectively referred to as pattern recognition receptors (PRR), including Scavenger receptors (SR) and Toll-like receptors (TLR), which recognize conserved structures on microbes. Recognition of pathogens by PRR on macrophages leads to an inflammatory response and is followed by secretion of various bactericidal molecules, including secreted phospholipase A2 (sPLA2), phagocytosis, processing of antigens and subsequent presentation on MHC molecules. Thus, PRR on macrophages play an important role in the protection against invading microorganisms by linking the innate and adaptive parts of the immune system. Importantly, these responses are tightly regulated by a set of inhibitory receptors, including the Siglecs.
Surprisingly little is known, however, about mechanisms by which pathogenic microbes manipulate/evade host PRR or secreted anti-bacterial molecules to circumvent the immune response and establish infections. The main focus of our research is on newly discovered mechanisms by which two clinically important bacteria, Streptococcus pyogenes and the group B streptococcus (GBS), utilize well-characterized surface virulence factors to evade innate immune receptors on macrophages and secreted anti-bacterial molecules. We are mainly studying the role of these subversion mechanisms on the outcome of 1) phagocytosis, 2) inflammatory response, 3) resistance to killing by anti-bacterial molecules and 4) the ability of streptococci to establish infections.
The molecular mechanisms by which pathogenic bacteria manipulate PRR on macrophages and resist anti-bacterial molecules are potential targets for novel therapies against infectious diseases. These mechanisms may also reveal novel ways to modulate the inflammatory response/activation of macrophages, information that may be highly relevant for the development of novel treatments against autoimmune/rheumatic diseases.
5 recent original publications
Movert, E., Wu, Y., Lambeau, G., Touqui, L., and Areschoug, T.
A novel bacterial resistance mechanism against human group IIA secreted phospholipase A2: role of Streptococcus pyogenes Sortase A
J. Immunol. 2011; 187: 6437-46
Nordström, T., Movert, E., Olin, A.I., Ali, S.R., Nizet, V., Varki, A., and Areschoug, T.
Human Siglec-5 inhibitory receptor and immunoglobulin A (IgA) have separate binding sites in streptococcal beta protein
J. Biol. Chem. 2011; 286: 33981-91
Carlin, A. F., Chang, Y.C. Areschoug, T., Lindahl, G., Hurtado-Ziola, N., King, C. C., Varki, A., and Nizet, V.
Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5.
J. Exp. Med. 2009; 206: 1691-99
Areschoug, T., and Gordon, S.
Scavenger receptors: role in innate immunity and microbial pathogenesis.
Cell. Microbiol. 2009; 11: 1160-69
Areschoug, T., Waldemarsson, J., and Gordon, S.
Evasion of macrophage scavenger receptor A-mediated recognition by pathogenic streptococci.
Eur. J. Immunol. 2008; 38: 3068-79
Further publications here (new window)
|Total financing:||2.0 MSEK||Gov grant for clinical research ("ALF"):||1.0 MSEK|
|Total external financing:||1.0 MSEK||Natl and intl prioritized grants:||0.0 MSEK|