NOD-Like Receptors in Lung Diseases

Abstract

The lung is a particularly vulnerable organ at the interface of the body and the exterior environment. It is constantly exposed to microbes and particles by inhalation. The innate immune system needs to react promptly and adequately to potential dangers posed by these microbes and particles, while at the same time avoiding extensive tissue damage. Nucleotide-binding oligomerization domain-like receptors (NLRs) represent a group of key sensors for microbes and damage in the lung. As such they are important players in various infectious as well as acute and chronic sterile inflammatory diseases, such as pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury/acute respiratory distress syndrome, pneumoconiosis, and asthma. Activation of most known NLRs leads to the production and release of pro-inflammatory cytokines, and/or to the induction of cell death. We will review NLR functions in the lung during infection and sterile inflammation.

Keywords: NOD-like receptors; inflammasome; lung; lung injury; pneumonia.

Figure 1

Summary of the main characteristics of the NLRs. ^h and ^m symbolized a characteristic specific to human or mouse. For more details, refer to the main text.

Figure 2

Representation of NLRs involved in lung infections. Various lung pathogens can be sensed by different NLR. These NLRs either form inflammasomes to regulate IL-1 family cytokines and pyroptotic cell death, stimulate production of NF-κB-dependent inflammatory mediators, regulate autophagy, or control ROS production.