Rationale and Aims The Inflammation and Innate Immunity Research Cluster serves as the intellectual home for EHSRC members whose research is focused on mechanisms of immune responses. Although the expertise of many of its members is centered on airway inflammation, others focus on innate mechanisms relevant to systemic or more generally applicable immune responses. Some of these studies are directly linked with environmental exposures (e.g. transduction of the effects of endotoxin inhalation;environmental risk factors for systemic disorders such as sarcoidosis), whereas others relate to modulation of innate immune responses (e.g. the properties of beta-defensins and other innate immune response elements;effects of histamine on airway epithelial permeability) or host susceptibility to environmentally encountered agents (e.g. the role of biofilms in modulating response to inhaled bacteria). The research cluster members have a long history of investigations in basic airway and inflammation biology, and have been responsible for an important body of work that has advanced our understanding of how innate immune system responses modulate the effects of environmental agents, such as microbial products. These products have an important effect on rural and environmental health, and they have been implicated in the development of both adverse health consequences (for example, progressive accelerated decline of respiratory function among workers occupationally exposed in animal confinement facilities) and protective responses (for example, as codified in the hygiene hypothesis, the reduced risk of atopy and allergic airway inflammation among those raised on a farm). The goals of the Inflammation and Innate Immunity Research Cluster are to enhance the development of new science related to environmental lung disease, and to promote the use of research findings to reduce the adverse health effects of environmental contaminants among rural and agricultural populations. The aims of the Cluster are to: Aim 1) Promote investigations into inflammatory and immune mechanisms relevant to and responsible for the health effects of agricultural and rural exposures; Aim 2) Promote and enhance training in the disciplines of inflammation and immunology that are relevant to environmentally-related lung disease;encourage trainees to pursue studies in related areas of research; Aim 3) Serve as a national resource in inflammation and immunology for mechanistic studies related to agricultural and rural exposures.