[mtwalsh01]

Bacterial evasion methods and toll-like receptors

The previous article details some of the methods by which bacteria evade the immune system, including the innate immune system. Key to the innate immune system are pattern recognition receptors, which recognise conserved molecular motifs in pathogens. They include the family of Toll-like receptors (TLR) which recognise conserved motifs known as pathogen-associated molecular patterns (PAMPs). There are currently ten known human TLRs. The majority, i.e. TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9, TLR10 and TLR11, recognise bacterial PAMPs found for example on lipopolysaccharide (LPS), flagellin, CpG oligonucleotides and uropathogenic bacteria. These interactions are mediated by Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and adaptor proteins. Recognition of PAMPs by TLRs results in signalling cascades with activation of transcription factors and cellular responses including the production of inflammatory mediators such as interferons (IFNs) and cytokines. This helps initiate the innate immune response.

Some bacteria have evolved novel methods of evading TLRs. For example, bacterial TIR domains have been identified in many pathogenic bacteria including Salmonella enterica serovar Enteritidis, Brucella sp, uropathogenic E. coli and Yersinia pestis. Studies suggest that they can interfere directly with the TLR signalling pathway but by different methods. P. aeruginosa, a bacteria whose presence is associated with poor prognosis in cystic fibrosis (CF) patients displays down-regulation of flagellar expression, thus losing motility, evading phagocytic receptors that recognize flagellar components and evading flagellin-mediated TLR5 signaling. TLR4 recognises the hexa-acylated form of the lipid A component of LPS. Hexa-acylated lipid A is conserved among many Gram-negative bacteria, allowing them to be recognised by TLR4 and targeted by the innate immune responses. However, in some bacterial species less-acylated forms of lipid A have been observed which are poor stimulators of TLR4. It is hypothesised that these modifications could facilitate evasion of the innate immune response, and increase pathogenicity of bacteria including Yersinia pestis, Francisella tularensis, Helicobacter pylori, and Porphyromonas gingivalis. Further studies are needed on this phenomenon.

It is clear that bacteria are constantly evolving methods to evade the host immune response at all stages. Further studies are needed in the constant battle.

Sources

http://www.ebioscience.com/knowledge-cen...eptors.htm

http://www.invivogen.com/review-tlr

AMIEL, E. et al., 2010. Pseudomonas aeruginosa evasion of phagocytosis is mediated by loss of swimming motility and is independent of flagellum expression. Infection and immunity, 78(7), pp. 2937-2945

MATSUURA, M., 2013. Structural Modifications of Bacterial Lipopolysaccharide that Facilitate Gram-Negative Bacteria Evasion of Host Innate Immunity. Frontiers In Immunology, 4, pp. 109-109

RANA, R.R. et al., 2013. Bacterial TIR-containing proteins and host innate immune system evasion. Germany: Springer-Verlag.

HARTL, D. et al., 2012. Innate immunity in cystic fibrosis lung disease. J Cyst Fibros. 11(5), pp. 363-82.