Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 38, Issue 4, Pages 401-406Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2007-0309OC
Keywords
Fc gamma receptors; host defense; bacterial infection; Pseudomonas; pneumonia
Funding
- NHLBI NIH HHS [HL51366] Funding Source: Medline
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Defenses against bacterial infections involve activation of multiple systems of innate immunity, including complement, Toll-like receptors, and defensins. Reactions to chronic infections bring adaptive immune mechanisms into play as well, with the introduction of modulatory interactions between the two. In humans with chronic lung infections, the severity of inflammation and disease correlate with elevated levels of pathogen-specific immune complexes and complement activation. In mice with genetic deficiency in C5, or targeted deletion of the C5a receptor, Pseudomonas lung infections reveal a role for the C5a anaphylatoxin in disease severity. Deficient animals exhibit significantly reduced survival and clearance of infecting bacteria, simultaneous with greatly increased pulmonary influx of inflammatory cells. Among the actions of C5a on inflammatory cells mediated through the C5a receptor is a shift in the relative expression of Fc gamma receptors to increase Fc gamma RIII relative to Fc gamma RII. This shift may significantly impact defenses against chronic infection, reflecting the cellular activation profiles of these IgG receptors. We addressed the role of Fc gamma RIII in defense against Pseudomonas lung infection, and found that, like C5aR-deficient mice, animals with targeted deletion of Fc gamma RIII are more susceptible to mortality upon infection and exhibit reduced clearance of the pathogen. Pseudomonas infection was associated with an increase in the Fc gamma RIII/Fc gamma RII ratio in wild-type mice, and the data support its role as an additional mechanism of host defense against bacterial infection.
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