The nucleotide-binding domain, leucine-rich repeat protein 3 inflammasome/IL-1 receptor I axis mediates innate, but not adaptive, immune responses after exposure to particulate matter under 10 μm

Am J Respir Cell Mol Biol. 2015 Jan;52(1):96-105. doi: 10.1165/rcmb.2014-0158OC.


Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. Inhaled PM induces innate immune responses by airway epithelial cells that may lead to the exacerbation or de novo development of airway disease. We have previously shown that 10-μm PM (PM10) activates the nucleotide-binding domain, leucine-rich repeat protein (NLRP) 3 inflammasome in human airway epithelial cells. Our objective was to determine the innate and adaptive immune responses mediated by the airway epithelium NLRP3 inflammasome in response to PM10 exposure. Using in vitro cultures of human airway epithelial cells and in vivo studies with wild-type and Nlrp3(-/-) mice, we investigated the downstream consequences of PM10-induced NLPR3 inflammasome activation on cytokine production, cellular inflammation, dendritic cell activation, and PM10-facilitated allergic sensitization. PM10 activates an NLRP3 inflammasome/IL-1 receptor I (IL-1RI) axis in airway epithelial cells, resulting in IL-1β, CC chemokine ligand-20, and granulocyte/macrophage colony-stimulating factor production, which is associated with dendritic cell activation and lung neutrophilia. Despite these profound innate immune responses in the airway epithelium, the NLRP3 inflammasome/IL-1RI axis is dispensable for PM10-facilitated allergic sensitization. We demonstrate the importance of the lung NLRP3 inflammasome in mediating PM10 exposure-associated innate, but not adaptive, immune responses. Our study highlights a mechanism by which PM10 exposure can contribute to the exacerbation of airway disease, but not PM10-facilitated allergic sensitization.

Keywords: air pollution; airway epithelium; allergic sensitization; asthma; human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Asthma / chemically induced
  • Asthma / immunology
  • Asthma / pathology
  • Carrier Proteins / immunology*
  • Cell Line, Transformed
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Humans
  • Immunity, Innate / drug effects*
  • Inflammasomes / immunology
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Particulate Matter / adverse effects*
  • Particulate Matter / pharmacology
  • Receptors, Interleukin-1 Type I / immunology*
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / pathology
  • Signal Transduction / immunology*


  • Carrier Proteins
  • Cytokines
  • IL1R1 protein, human
  • IL1R1 protein, mouse
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • Particulate Matter
  • Receptors, Interleukin-1 Type I