Toll-like receptors in the host defense against Pseudomonas aeruginosa respiratory infection and cystic fibrosis

Abstract

TLRs function in innate immunity by detecting conserved structures present in bacteria, viruses, and fungi. Although TLRs do not necessarily distinguish pathogenic organisms from commensals, in the context of compromised innate immunity and combined with pathogens' effector molecules, TLRs drive the host response to the organism. This review will discuss the evidence and role(s) of TLRs in the response to the opportunistic bacterial pathogen, Pseudomonas aeruginosa, as it relates to respiratory infection and CF, in which innate immune mechanisms are indeed compromised. Outer membrane lipoproteins, LPS, flagellin, and nucleic acids all serve as ligands for TLR2, -4, -5, and -9, respectively. These TLRs and their respective downstream effector molecules have proven critical to the host response to P. aeruginosa, although the protective effects of TLRs may be impaired and in some cases, enhanced in the CF patient, contributing to the particular susceptibility of individuals with this disease to P. aeruginosa infection.

Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication

“…Zymosan is a common PAMPs expressed by yeast, and functions as a ligand of TLR2 [39]. TLR2 can also be activated by lipoproteins or lipopeptides located on the outer membrane of PA [40] and other pathogens [41]. It is reported that activation of TLR2 enhanced autophagy of L. monocytogenes [41].…”

Enhanced immune response of BMDCs pulsed with H9N2 AIV and CpG

“…Initiation of a protective immune defence against a particular pathogen requires that the pathogen be processed efficiently by the immune system [24]. Although the conventional inactive H9N2 vaccines play a protective role to against H9N2 in certain extent, but their protective effect in eliminating clinical signs of illness do not compare with H9N2 vaccine.…”

Membrane lipids and cell signaling

“…Alterations in fatty acid saturation is a key property that controls stiffness and elasticity of PMs, and is a well-known mechanism for adaptation to distinct temperatures. It has been previously shown that polyunsaturated fatty acids (PUFAs) can impair lipopolysaccharide (LPS)-mediated activation of TLR4 which eventually promotes the activation of the nuclear factor kappa B (NFkB) [25]. Nonetheless, the mechanisms associated with this process have remained elusive until recently.…”