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Infection and inflammation during contact lens wear is often associated with microbial contamination of lenses. Several different types of microbes that colonize lenses can lead to infection and inflammation, but the most common cause of infection (microbial keratitis; MK) remains the Gram-negative bacterium Pseudomonas aeruginosa. P. aeruginosa has a battery of cell-associated and extracellular virulence factors it can use to initiate and maintain infection. Its ability to produce proteases, to either invade or kill corneal cells, and to coordinate expression of virulence factors via quorum-sensing have been shown to be important during MK. Another important factor that contributes to the destruction of the cornea during MK is excessive activation of the host defense system. P. aeruginosa can activate several pathways of the immune system during MK, and activation often involves receptors on the corneal epithelial cells called toll-like receptors (TLRs). These TLRs recognize e.g., lipopolysaccharide or flagella from P. aeruginosa and activate the epithelial cells to produce inflammatory mediators such as cytokines and chemokines. These cytokines or chemokines recruit white blood cells, predominantly polymorphonuclear leukocytes, to the infection in order that they can phagocytose and kill the P. aeruginosa. However, continued recruitment and presence of these polymorphonuclear neutrophils and other white blood cells in the corneal tissue leads to destruction of corneal cells and tissue components. This can ultimately lead to scarring and vision loss.