Neutrophil chemotaxis by pathogen-associated molecular patterns -: formylated peptides are crucial but not the sole neutrophil attractants produced by Staphylococcus aureus

被引:40
作者
Dürr, MC
Kristian, SA
Otto, M
Matteoli, G
Margolis, PS
Trias, J
van Kessel, KP
van Strijp, JA
Bohn, E
Landmann, R
Peschel, A [1 ]
机构
[1] Univ Tubingen, Med Microbiol & Hyg Dept, Tubingen, Germany
[2] Univ Basel Hosp, Dept Res, Div Infect Dis, CH-4031 Basel, Switzerland
[3] NIAID, Lab Human Bact Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA
[4] Vicuron Pharmaceut Inc, Fremont, CA USA
[5] Univ Utrecht, Eijkman Winkler Inst, Ctr Med, Utrecht, Netherlands
关键词
D O I
10.1111/j.1462-5822.2005.00610.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The chemotactic migration of phagocytes to sites of infection, guided by gradients of microbial molecules, plays a key role in the first line of host defence. Bacteria are distinguished from eukaryotes by initiation of protein synthesis with formyl methionine. Synthetic formylated peptides (FPs) have been shown to be chemotactic for phagocytes, leading to the concept of FPs as pathogen-associated molecular patterns (PAMPs). However, it remains unclear whether FPs are major chemoattractants released by bacteria and whether further chemoattractants are produced. A Staphylococcus aureus mutant whose formyltransferase gene was inactivated (Delta fmt) produced no FPs and the in vitro and in vivo ability of Delta fmt culture supernatants to recruit neutrophils was considerably reduced compared with those of the parental strain. However, some chemotactic activity was retained, indicating that bacteria produce also unknown, non-FP chemoattractants. The activity of these novel PAMPs was sensitive to pertussis toxin but insensitive to the formyl peptide receptor inhibitor CHIPS. Delta fmt culture supernatants caused reduced calcium ion fluxes and reduced CD11b upregulation in neutrophils compared with wild-type supernatants. These data demonstrate an important role of FPs in innate immunity against bacterial infections and indicate that host chemotaxis receptors recognize a larger set of bacterial molecules than previously thought.
引用
收藏
页码:207 / 217
页数:11
相关论文
共 35 条
[1]   A SERIES OF SHUTTLE VECTORS FOR BACILLUS-SUBTILIS AND ESCHERICHIA-COLI [J].
BRUCKNER, R .
GENE, 1992, 122 (01) :187-192
[2]   Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent [J].
de Haas, CJC ;
Veldkamp, KE ;
Peschel, A ;
Weerkamp, F ;
Van Wamel, WJB ;
Heezius, ECJM ;
Poppelier, MJJG ;
Van Kessel, KPM ;
van Strijp, JAG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (05) :687-695
[3]  
Foster TJ, 1998, METHOD MICROBIOL, V27, P433
[4]   Subinhibitory concentrations of the deformylase inhibitor actinonin increase bacterial release of neutrophil-activating peptides: a new approach to antimicrobial chemotherapy [J].
Fu, HM ;
Dahlgren, C ;
Bylund, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (08) :2545-2550
[5]   Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse [J].
Gao, JL ;
Chen, H ;
Filie, JD ;
Kozak, CA ;
Murphy, PM .
GENOMICS, 1998, 51 (02) :270-276
[6]   Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor [J].
Gao, JL ;
Lee, EJ ;
Murphy, PM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (04) :657-662
[7]   Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents [J].
Giglione, C ;
Pierre, M ;
Meinnel, T .
MOLECULAR MICROBIOLOGY, 2000, 36 (06) :1197-1205
[8]   Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing [J].
Girardin, SE ;
Hugot, JP ;
Sansonetti, PJ .
TRENDS IN IMMUNOLOGY, 2003, 24 (12) :652-658
[9]   DISRUPTION OF THE GENE FOR MET-TRANSFER RNA F-MET FORMYLTRANSFERASE SEVERELY IMPAIRS GROWTH OF ESCHERICHIA-COLI [J].
GUILLON, JM ;
MECHULAM, Y ;
SCHMITTER, JM ;
BLANQUET, S ;
FAYAT, G .
JOURNAL OF BACTERIOLOGY, 1992, 174 (13) :4294-4301
[10]   Toll receptors in innate immunity [J].
Imler, JL ;
Hoffmann, JA .
TRENDS IN CELL BIOLOGY, 2001, 11 (07) :304-311