Toll like receptor-2 modulates both innate and adaptive immune responses during chronic fungal asthma in mice.
OBJECTIVE
We investigated the effect of TLR2 gene deletion in a murine model of chronic fungal asthma.


METHODS
TLR2 wildtype (TLR2(+/+)) and TLR2 deficient (TLR2(-/-)) mice were sensitized to soluble A. fumigatus antigens and challenged with live A. fumigatus conidia, and the extent of allergic airways disease was analyzed in both groups of mice at 3, 7, 14, and 30 days after conidia.


RESULTS
At day 7 post-conidia, TLR2(-/-) mice exhibited significantly lower airway hyperresponsiveness, airway inflammation, and whole lung Th2 cytokine levels compared with the TLR2(+ / +) group. TLR2 deletion also significantly reduced mucus cell metaplasia and peribronchial fibrosis at day 30 after conidia. However, fungal material persisted in the TLR2(-/-) group, and at day 30 after conidia TLR2(-/-) mice exhibited enhanced airway neutrophil recruitment and airway hyperresponsiveness.


CONCLUSIONS
Thus, during chronic fungal asthma in mice, TLR2 is a major contributor to the maintenance of the adaptive Th2-cytokine driven and anti-fungal innate responses.
Buckland
K F
KF
Immunology Program, Department of Pathology, University of Michigan Medical School, Rm 4057, BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
O'Connor
E
E
Murray
L A
LA
Hogaboam
C M
CM
D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000166:cytology / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000382:microbiology; D054426:Chemokine CXCL2 / Q000276:immunology; D005260:Female; D005355:Fibrosis; D007113:Immunity, Innate / Q000502:physiology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma