Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans.
BACKGROUND
Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is considered to be important for an appropriate immune response against pathogens that enter the lower airways.


OBJECTIVE
We studied the effects of two different TLR agonists relevant for respiratory infections in the human lung: lipoteichoic acid (LTA; TLR2 agonist, component of gram-positive bacteria) and lipopolysaccharide (LPS; TLR4-agonist, component of gram-negative bacteria).


METHODS
Fifteen healthy subjects were given LPS or LTA: by bronchoscope, sterile saline was instilled into a lung segment followed by instillation of LTA or LPS into the contralateral lung. After 6 hours, a bronchoalveolar lavage was performed and inflammatory parameters were determined. Isolated RNA from purified alveolar macrophages was analyzed by multiplex ligation-dependent probe amplification. In addition, spontaneous cytokine release by alveolar macrophages was measured.


RESULTS
Marked differences were detected between LTA- and LPS-induced lung inflammation. Whereas both elicited neutrophil recruitment, only LPS instillation was associated with activation of neutrophils (CD11b surface expression, degranulation product levels) and consistent rises of chemo-/cytokine levels. Moreover, LPS but not LTA activated alveolar macrophages, as reflected by enhanced expression of 10 different mRNAs encoding proinflammatory mediators and increased spontaneous cytokine release upon incubation ex vivo. Remarkably, only LTA induced C5a release.


CONCLUSIONS
This is the first study to report the in vivo effects of LTA in men and to compare inflammation induced by LTA and LPS in the human lung. Our data suggest that stimulation of TLR2 or TLR4 results in differential pulmonary inflammation, which may be of relevance for understanding pathogenic mechanisms at play during gram-positive and gram-negative respiratory tract infection.
Hoogerwerf
Jacobien J
JJ
Center for Infection and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands. j.j.hoogerwerf@amc.uva.nl.
de Vos
Alex F
AF
Bresser
Paul
P
van der Zee
Jaring S
JS
Pater
Jennie M
JM
de Boer
Anita
A
Tanck
Michael
M
Lundell
Daniel L
DL
Her-Jenh
Chung
C
Draing
Christian
C
von Aulock
Sonja
S
van der Poll
Tom
T
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D020869:Gene Expression Profiling; D006094:Gram-Positive Bacteria; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009504:Neutrophils; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology*; D013211:Staphylococcus aureus; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051197:Toll-Like Receptor 4 / Q000819:agonists*
D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid