Pseudomonas aeruginosa is the major cause of chronic pulmonary disease in cystic fibrosis (CF) patients. During chronic infection, P. aeruginosa lose certain virulence factors, transform into a mucoid phenotype, and develop antibiotic resistance. We hypothesized that these genetic and phenotypic alterations of P. aeruginosa affect the airway epithelial responses. A549 cells were infected with 27 well-characterized isolates of P. aeruginosa from CF patients obtained during longitudinal observation, or with P. aeruginosa mutant strains lacking flagella, pili, lipopolysaccharide, or pyocyanin. Pseudomonas aeruginosa isolates from the early stages of the infection exhibited high adherence to A549 cells, were readily internalized, and able to induce reactive oxygen species (ROS) production, apoptosis of infected cells, and the release of granulocyte macrophage colonystimulating factor. Late P. aeruginosa isolates collected from patients with chronic lung infection were shown to have reduced adherence to and internalization into A549 cells compared with bacteria from patients with intermittent P. aeruginosa colonization, and induced lower production of ROS and apoptosis, but caused high proinflammatory cytokine and adhesion molecule expression. Our findings suggest that despite the loss of virulence factors during the adaptation process in the CF lung by late P. aeruginosa strains, they retain high proinflammatory abilities that likely contribute to the disease pathogenesis.

ABSTRACTPrior to the introduction ofHaemophilus influenzaetype b (Hib) conjugate vaccines, invasive Hib disease affected almost exclusively children. According to some recent studies, in the postvaccine era, adults, the elderly, and immunocompromised persons can be affected more often than children. As the production of type-specific anti-capsular polysaccharide antibodies is the major defense mechanism against Hib, individuals with defects in humoral immune responses have high susceptibility to infections caused by Hib. We hypothesized that nonvaccinated adults with chronic conditions causing immunosuppression may lack protective antibody to Hib. We assessed serum anti-Hib IgG levels and bactericidal activity in 59 patients with chronic renal failure, 30 patients with type 2 diabetes mellitus, 28 patients with chronic obstructive pulmonary disease (COPD), and 20 patients with multiple myeloma compared to 32 healthy controls of similar age. Considering antibody at >0.15 μg/ml as the protective correlate in unvaccinated individuals, we detected subprotective Hib antibody levels in 29% of chronic renal failure, 20% of diabetes, 14% of COPD, and 55% of myeloma patients compared to 3% of healthy controls. Additionally, 70% of myeloma and 58% of chronic renal failure patients did not have detectable serum bactericidal activity against Hib. Among individuals with severe diseases causing secondary immunodeficiency, patients with multiple myeloma and chronic renal failure are at an increased risk of invasive Hib disease. Considering that Hib continues to circulate in the population, this study provides a rationale for the immunization of some adult patients with secondary immunodeficiency with the pediatric Hib vaccine to achieve protective immunity.

Integrins are a large family of heterodimeric transmembrane cell adhesion receptors. During the last decade, it has become clear that integrins significantly participate in various host-pathogen interactions involving pathogenic bacteria, fungi, and viruses. Many bacteria possess adhesins that can bind either directly or indirectly to integrins. However, there appears to be an emerging role for integrins beyond simply adhesion molecules. Given the conserved nature of integrin structure and function, and the diversity of the pathogens which use integrins, it appears that they may act as pattern recognition receptors important for the innate immune response. Several clinically significant bacterial pathogens target lung epithelial integrins, and this review will focus on exploring various structures and mechanisms involved in these interactions.