The Role of Innate Immunity in Pulmonary Infections

Figure 2

Overview of NLRs and RIG-I involved in pulmonary infections. Various lung pathogens are sensed by different NLRs. Cytosolic NOD1 and NOD2 recognize bacterial peptidoglycans (iE-DAP and MDP). After pulmonary pathogen activation, Nod1 and Nod2 activate downstream NF-κB and MAPK through recruiting the serine-threonine kinase RIP2, leading to the production of proinflammatory cytokines, chemokines, and adhesion molecules. When stimulated by pulmonary bacterial pathogens, those molecules oligomerize to form the inflammasome, consisting of NLRP, ASC, and pro-caspase-1, which in turn cleaves pro-caspase 1 into its active form. Active caspase-1 can than cleaves the pro forms of IL-1β and IL-18 into their respective mature cytokines leading to inflammation and/or initiate pyroptosis. NOD: nucleotide-binding and oligomerization domain; NLR: nucleotide-associated oligomerization domain-like receptor; NLRP: NOD-like receptor proteins; iE-DAP: γ-D-Glu-mDAP; NLRC4: NOD-, LRR,- and CARD domain-containing-4; MD: MurNAc-L-Ala-D-isoGln; NF-κB: nuclear factor-κB; MAPKs: mitogen-activated protein kinases; ssRNA: single-stranded RNA; ASC: apoptosis-associated speck-like protein; CARD: caspase recruitment domain; PYD: pyrin domain; RIP2: receptor interacting protein 2; LRR: leucine-rich repeat; C. pneumonia: Cryptococcus pneumoniae; B. pseudomallei: Burkholderia pseudomallei; C. neoformans: Cryptococcus neoformans; F. tularensis: Francisella tularensis; K. pneumoniae: Klebsiella pneumoniae; M. catarrhalis: Moraxella catarrhalis; P. brasiliensis: Paracoccidioides brasiliensis; Bacillus anthracis: B. anthracis.