The lung responds to zymosan in a unique manner independent of toll-like receptors, complement, and dectin-1.
In vitro studies indicate that the inflammatory response to zymosan, a fungal wall preparation, is dependent on Toll-like receptor (TLR) 2, and that this response is enhanced by the dectin-1 receptor. Complement may also play an important role in this inflammatory response. However, the relevance of these molecules within the in vivo pulmonary environment remains unknown. To examine pulmonary in vivo inflammatory responses of the lung to zymosan, zymosan was administered by intratracheal aerosolization to C57BL/6, TLR2- TLR4-, MyD88-, and complement-deficient mice. Outcomes included bronchoalveolar fluid cell counts. We next examined effects of dectin-1 inhibition on response to zymosan in alveolar macrophages in vitro and in lungs of C57BL/6, TLR2-, and complement-deficient mice. Finally, the effect of alveolar macrophage depletion on in vivo pulmonary responses was assessed. Marked zymosan-induced neutrophil responses were unaltered in TLR2-deficient mice despite a TLR2-dependent response seen with synthetic TLR2 agonists. TLR4, MyD88, and complement activation were not required for the inflammatory response to zymosan. Although dectin-1 receptor inhibition blocked the inflammatory response of alveolar macrophages to zymosan in vitro, in vivo pulmonary leukocyte recruitment was not altered even in the absence of TLR2 or complement. Depletion of alveolar macrophages did not affect the response to zymosan. Neither complement, macrophages, nor TLR2, TLR4, MyD88, and/or dectin-1 receptors were involved in the pulmonary in vivo inflammatory response to zymosan.
Kelly
Margaret M
MM
Immunology Research Group, Department of Physiology, University of Calgary, Room 1863, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1 Canada.
McNagny
Kelly
K
Williams
David L
DL
van Rooijen
Nico
N
Maxwell
Lori
L
Gwozd
Carol
C
Mody
Christopher H
CH
Kubes
Paul
P
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003165:Complement System Proteins / Q000502:physiology*; D037181:Lectins, C-Type; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology*; D000099181:Dectin-1
D003165:Complement System Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051193:Toll-Like Receptors; D015054:Zymosan; D000099181:Dectin-1