Premium
Gut Commensal Flora and the Inflammasome Modulate the Sterile Inflammatory Response to Ventilated Lung Ischemia Reperfusion (IR)
Author(s) -
Prakash Arun,
Tian Xiaoli,
Hellman Judith
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.863.7
Subject(s) - inflammatory response , inflammasome , flora (microbiology) , lung , inflammation , medicine , biology , immunology , bacteria , genetics
Background Lung ischemia reperfusion (IR) injury is a result of inflammation that occurs when pulmonary blood flow is temporarily interrupted, such as during hemorrhagic trauma, thromboembolic disease, or transplantation. Understanding the mechanisms underlying this process may provide new therapeutic approaches to limit lung injury when appropriate. We previously demonstrated a role for TLR4 and alveolar macrophages in lung IR injury. We tested the hypothesis that gut commensal flora and inflammasome pathways regulate inflammation induced by lung IR. Methods: We probed the inflammatory response following left pulmonary artery occlusion in wild‐type mice, and characterized the role of the inflammasome using knockout mice. To investigate the influence of gastrointestinal commensal flora on the inflammatory response to lung IR, mice were pretreated with intestinally‐localized antibiotics, and then subjected to lung IR. Results: We observed that intestinal commensal flora modulate the inflammatory response to lung IR in vitro and in vivo. Alveolar macrophages collected from antibiotic‐fed mice had reduced induction of inflammation by TLR agonists. Furthermore, as compared with control mice, antibiotic‐fed mice had significantly attenuated recruitment of infiltrating neutrophils and diminished lung edema. Circulating products or metabolites from commensal flora may thus maintain alveolar macrophages in a primed state to respond to lung IR. Alternatively, this effect could me mediated by intestinal lymphoid tissue. We also discovered distinct lung IR responses in ASC, NLRP3, and NLRC4ko mice implicating a role for the inflammasome in lung IR inflammation. Research Support: UCSF Departmental Funds.