Airway epithelial cells are the first line of defense against invading microbes, and they protect themselves through the production of carbohydrate and protein matrices concentrated with antimicrobial products. In addition, they act as sentinels, expressing pattern recognition receptors that become activated upon sensing bacterial products and stimulate downstream recruitment and activation of immune cells which clear invading microbes. Bacterial pathogens that successfully colonize the lungs must resist these mechanisms or inhibit their production, penetrate the epithelial barrier, and be prepared to resist a barrage of inflammation. Despite the enormous task at hand, relatively few virulence factors coordinate the battle with the epithelium while simultaneously providing resistance to inflammatory cells and causing injury to the lung. Here we review mechanisms whereby airway epithelial cells recognize pathogens and activate a program of antibacterial pathways to prevent colonization of the lung, along with a few examples of how bacteria disrupt these responses to cause pneumonia. 1. Introduction Host defense in the mammalian lung relies heavily on innate immune mechanisms that prevent invasion of pathogens. The airway epithelium is the front line defender of the lung which signals recruitment and activation of effector cells to kill invading pathogens and provides a physical barrier loaded with antibacterial compounds. Bacteria that successfully penetrate the epithelium must have the capability to evade these mechanisms, which typically means they avoid recognition and killing by both the effector cells of the innate immune system and the antimicrobial mechanisms in the epithelium. Pneumonia is a consequence of lung colonization, pathogen-induced injury to the epithelium, sustained activation of inflammation, and overactivation of tissue repair mechanisms. Furthermore, vascular leakage and edema are caused by these host responses, allowing the pathogen to gain access to the blood, where it may spread systemically and cause sepsis. Bronchopneumonia is characterized by focal areas of congestion of the parenchyma by bacteria, inflammatory cells, and fibrin while lobar pneumonia is defined by a single area of congestion that takes up a larger portion of a lung lobe. Interstitial pneumonia involves congestion in the surrounding vasculature and is typically the result of overactive recruitment of inflammatory cells. In this paper, we will discuss how airway epithelial cells orchestrate innate immune responses in the lungs in order to limit invasion of
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