Submitted on August 18, 2005
Accepted on January 31, 2006
Ablation of the Complement C3a Anaphylatoxin Receptor Causes Enhanced Killing of Pseudomonas aeruginosa in a Mouse Model of Pneumonia
Stacey L Mueller-Ortiz1, Travis J Hollmann1, David L Haviland1, and Rick A Wetsel1*
1 Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: Rick.A.Wetsel{at}uth.tmc.edu.
The C3a anaphylatoxin is a 77 amino acid peptide that is generated by enzymatic cleavage of C3 during activation of the complement system. C3a mediates numerous biological functions on binding its receptor (C3aR), which is present on both myeloid and nonmyeloid cells. To investigate the biological impact of C3a-mediated effects during acute pneumonia caused by Pseudomonas aeruginosa, C3aR-deficient mice and matched wild-type (WT) mice were subjected to P. aeruginosa pulmonary infection. C3aR-deficient mice exhibited increased killing of P. aeruginosa in the lungs, less dissemination of bacteria into the bloodstream, and a decreased inflammatory response to P. aeruginosa pulmonary infection compared to WT mice. To examine if the absence of C3aR would impact the humoral immune response to P. aeruginosa, WT and C3aR-deficient mice were immunized via intraperitoneal injection with live P. aeruginosa. Both groups of mice developed similar levels of antibody specific to P. aeruginosa. Immunized C3aR-deficient and WT mice were subjected to P. aeruginosa pulmonary infection, and C3aR-deficient mice again displayed increased killing of P. aeruginosa in the lungs, less dissemination of bacteria into the bloodstream, and a decreased inflammatory response in the lungs. Collectively, these data demonstrate that independent of antibody production, absence of C3aR causes enhanced killing of P. aeruginosa despite a diminished inflammatory response in a mouse model of pneumonia.
