title: Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections.
abstract: Pseudomonas aeruginosa remains one of the major clinical pathogens that burden immuno-compromised patients and patients with cystic fibrosis. The present study aimed to define the role of the lectin pathway of complement in the immune-defence against P. aeruginosa in a mouse model of invasive pneumonia. Using in vitro assays specific for each of the three complement pathways, we demonstrate that some strains of P. aeruginosa bind lectin pathway recognition sub-components and initiate complement activation in a lectin pathway-specific mode. All of the tested strains activated complement via classical and alternative pathways. We assessed the importance of lectin pathway activation in fighting P. aeruginosa infections by testing a lectin pathway activating strain in a mouse model of intra-nasal infection. MASP-2 (mannan binding lectin associated serine protease-2) deficient mice, which have no lectin pathway activity, had no significant survival disadvantage compared to wild type littermates (72.7% and 81.8% survival, respectively, p=0.48). Likewise, no difference in opsonising activity was seen between MASP-2 sufficient and MASP-2 deficient mouse sera. Moreover, cytokine expression profiles in the lungs of WT mice and MASP-2-/- mice were similar throughout the course of P. aeruginosa infection. We conclude that the lectin pathway does not play an essential role in fighting P. aeruginosa infection in mice.
authors: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors: Hany Ibrahim
authors: HI
authors: Kenawy
authors: Youssif Mohammed
authors: YM
authors: Ali
authors: Kumar
authors: K
authors: Rajakumar
authors: Nicholas J
authors: NJ
authors: Lynch
authors: Aras
authors: A
authors: Kadioglu
authors: Cordula M
authors: CM
authors: Stover
authors: Wilhelm J
authors: WJ
authors: Schwaeble
mesh_terms: D000818:Animals; D015922:Complement C1q / Q000276:immunology; D015935:Complement C4b / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000276:immunology; D003171:Complement Pathway, Classical / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D037102:Lectins; D010446:Peptide Fragments; D012333:RNA, Messenger; C033860:complement C4c; D015922:Complement C1q; D015935:Complement C4b; C491340:MASP-2 protein, mouse; D050606:Mannose-Binding Protein-Associated Serine Proteases