THE ROLE OF PSEUDOMONAS AERUGINOSA IN MODULATING HOST IMMUNE RESPONSES IN BIOFILM-ASSOCIATED CHRONIC INFECTIONS

Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium that may cause chronic disease, particularly in cystic fibrosis patients and individuals with compromised immunity. The virulence of P. aeruginosa, resistance to antimicrobials, as well as its ability to resist innate and adaptive host immunity, is largely attributed to its specialized ability to proliferate robust biofilms on medical devices and host tissues. Biofilms are dynamic, changeable, and continually promote local immune responses, in order to maintain microbe persistence and exist for the bacteria's benefit as protective niches. Infections caused by biofilms are different from acute infections, as they take on a slow, chronic course, overtime scales that can last from months to years. Filamentous microbes within biofilms can use an extracellular polymeric substance (EPS) matrix, which provides protection from antibiotics while simultaneously hindering the diffusion of crucial immune mediators. P. aeruginosa modifies the immune response of the host in several ways, including inhibiting the synthesis of certain proinflammatory cytokines, altering chemotactic signals, disrupting cellular recruitment to sites of infection, and modifying cellular activation. P. aeruginosa can utilize various approaches of immune modulation that can succeed in suppressing the host's immune response into chronic injury and inflammatory environment. P. aeruginosa use a number of mechanisms to evade the immune system including opportunistic quorum sensing, the release of exotoxins and enzymes, regulation of pattern recognition receptors & signaling cascades, and the inhibition of phagocytotic activity. These biofilms have a profound direct effect and impact on lung health in the form of cystic fibrosis, the blockage of airway, persistent airway inflammation, lung injury, and changes to lung ecology. Biofilms can modulate the immune responses related to recurrent infections, including chronic infections, thus prompting vital examination of current and traditional methods for treatment. New combination treatment approaches based on eradicating microbial infections plus restoring the host immunity (i.e. phage therapy, immune modulations, and antibiofilm agents), have been gaining attention over the past several years. A more complete understanding of biofilm immune evasions will be required to establish new antimicrobial agents or treatments that can synergize antimicrobial treatments with specific immune modulation.