TY - JOUR

T1 - Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

AU - Christophersen, L J

AU - Trøstrup, H

AU - Damlund, Dina Silke Malling

AU - Bjarnsholt, Thomas

AU - Thomsen, K

AU - Jensen, Peter Østrup

AU - Hougen, H P

AU - Høiby, N

AU - Moser, C

N1 - © 2012 British Society for Immunology.

PY - 2012

Y1 - 2012

N2 - Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by biofilms, tolerant to antibiotics and host responses. Instead, immune responses contribute to the tissue damage. However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P <0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P <0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P <0·0001). A shift from exclusively endobronchial to both parenchymal and endobronchial localization of inflammation from day 1 to days 2/3 (P <0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P <0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF) and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P <0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment.

AB - Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by biofilms, tolerant to antibiotics and host responses. Instead, immune responses contribute to the tissue damage. However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P <0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P <0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P <0·0001). A shift from exclusively endobronchial to both parenchymal and endobronchial localization of inflammation from day 1 to days 2/3 (P <0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P <0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF) and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P <0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment.

U2 - 10.1111/j.1365-2249.2012.04652.x

DO - 10.1111/j.1365-2249.2012.04652.x

M3 - Journal article

C2 - 23039893

VL - 170

SP - 222

EP - 230

JO - Clinical and Experimental Immunology, Supplement

JF - Clinical and Experimental Immunology, Supplement

SN - 0964-2536

IS - 2

M1 - 170

ER -