Review Article

Dampening Host Sensing and Avoiding Recognition in Pseudomonas aeruginosa Pneumonia

Figure 1

Pseudomonas aeruginosa recognition by PRRs during acute and chronic lung infection. (a) During acute lung infection, P. aeruginosa can invade, disseminate and lead to extensive tissue damage by means of potent array of extracellular and cell bound virulence factors. However the immunocompetent host mounts an effective immune response characterized of bacterial recognition by cell surface receptors, which are located on immune cells as well as epithelial cells. Plasma membrane-bound TLRs (TLR2, TLR4-MD2-CD14, TLR5, and TLR9) and cytosolic NLRs (NOD1, NOD2, and IPAF) recognise P. aeruginosa PAMPs and recruit adaptors to induce downstream signalling cascades, which result in transcription of pro-inflammatory mediators and mucins. These pro-inflammatory mediators, including chemokines, recruit immune cells to the lung in order to clear P. aeruginosa and resolve the infection. (b) During chronic lung infection, P. aeruginosa, enmeshed in biofilm structures, does not have direct contact to the airways epithelium and probably only immunogenic bacterial components can access to airway epithelium and immune cells in the lung. In addition, during long-term colonization, bacteria undergo a number of genetic changes and gain the ability to evade detection and clearance by the immune system, thus surviving in the host. The loss or modification of several PAMPs (flagellin, LPS, and PGN) lead to reduced recognition by TLRs and NLRs although components of the alginate capsule can still be recognized both by TLR2 and TLR4. The inadequate immune response may explain the chronic colonization of P. aeruginosa strains. NOD, Nucleotide-binding oligomerization domain; TLR, Toll-like receptor; NLR, Nod-like receptor; IPAF, ICE-protease activating factor; MyD88, myeloid differentiation primary response protein; CFTR, cystic fibrosis transmembrane conductance regulator.