title: CCR7 deficiency leads to leukocyte activation and increased clearance in response to pulmonary Pseudomonas aeruginosa infection.
abstract: CCR7 is a chemokine receptor expressed on the surfaces of T cells, B cells, and mature dendritic cells that controls cell migration in response to the cognate ligands CCL19 and CCL21. CCR7 is critical for the generation of an adaptive T cell response. However, the roles of CCR7 in the host defense against pulmonary infection and innate immunity are not well understood. We investigated the role of CCR7 in the host defense against acute pulmonary infection with Pseudomonas aeruginosa. We intranasally infected C57BL/6 mice with P. aeruginosa and characterized the expression of CCR7 ligands and the surface expression of CCR7 on pulmonary leukocytes. In response to infection, expression of CCL19 and expression of CCL21 were oppositely regulated, and myeloid dendritic cells upregulated CCR7 expression. We further examined the effects of CCR7 deficiency on the inflammatory response to P. aeruginosa infection. We infected Ccr7(-/-) and wild-type mice with P. aeruginosa and characterized the accumulation of pulmonary leukocytes, production of proinflammatory mediators, neutrophil activation, and bacterial clearance. CCR7 deficiency led to an accumulation of myeloid dendritic cells and T cells in the lung in response to infection. CCR7 deficiency resulted in higher expression of CD80 and CD86 on dendritic cells; increased production of interleukin-12/23p40 (IL-12/23p40), gamma interferon (IFN-gamma), and IL-1 alpha; increased neutrophil respiratory burst; and, ultimately, increased clearance of acute P. aeruginosa infection. In conclusion, our results suggest that CCR7 deficiency results in a heightened proinflammatory environment in response to acute pulmonary P. aeruginosa infection and contributes to more efficient clearance.
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, OH 45267-0056, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Eppert
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Motz
authors.forename: Brian W
authors.initials: BW
authors.lastname: Wortham
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Flury
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
mesh_terms: D000818:Animals; D054415:Chemokine CCL19 / Q000096:biosynthesis; D054421:Chemokine CCL21 / Q000096:biosynthesis; D015169:Colony Count, Microbial; D020869:Gene Expression Profiling; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*
chemical_list: C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7