Neutrophil chemotaxis by pathogen-associated molecular patterns--formylated peptides are crucial but not the sole neutrophil attractants produced by Staphylococcus aureus.
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 (Deltafmt) produced no FPs and the in vitro and in vivo ability of Deltafmt 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. Deltafmt 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.
Dürr
Manuela C
MC
Medical Microbiology and Hygiene Department, University of Tübingen, Tübingen, Germany.
Kristian
Sascha A
SA
Otto
Michael
M
Matteoli
Gianluca
G
Margolis
Peter S
PS
Trias
Joaquim
J
van Kessel
Kok P
KP
van Strijp
Jos A
JA
Bohn
Erwin
E
Landmann
Regine
R
Peschel
Andreas
A
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D005260:Female; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000502:physiology*
D039481:CD11b Antigen; D002630:Chemotactic Factors; D010455:Peptides; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019877:Hydroxymethyl and Formyl Transferases; D002118:Calcium