Can innate immunity be enhanced to treat microbial infections?

Abstract

Innate immunity is a highly effective set of conserved mechanisms used by multicellular organisms to recognize and counter the constant threat of microbial infections. There is evidence to indicate that innate responses are key to controlling most infections, as well as contributing to inflammatory responses that are central components of disease. In addition to Toll-like-receptor-mediated effects, many other mechanisms are used to recognize and respond to microbial threats. Natural molecules such as CpG DNA and small cationic peptides trigger innate responses that help to control infection. This indicates there is potential to utilize such compounds to activate or enhance innate responses as antimicrobials. Harnessing this activity, without associated harmful inflammatory responses, is the main challenge.

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Figure 1: Generalized major signal transduction pathway of TLR4.
Figure 2: Effects of cationic peptides on innate responses.
Figure 3: Effects mediated by CpG oligonucleotides.

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Acknowledgements

B.B.F. is a Howard Hughes Medical Institute (HHMI) International Research Scholar, a Canadian Institutes for Health Research (CIHR) Distinguished Investigator and the University of British Columbia Peter Wall Distinguished Professor. R.E.W.H. holds a Canada Research Chair. Operating grants from Genome Canada, with matching money from Inimex Pharmaceuticals, HHMI, CIHR, the Canadian Bacterial Diseases Network and the Canadian Cystic Fibrosis Foundation support work in their laboratories.

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Correspondence to B. Brett Finlay.

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Competing interests

The authors are co-founders of Inimex Pharmaceuticals Inc.

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DATABASES

Entrez

Helicobacter pylori

Listeria monocytogenes

Mycobacterium tuberculosis

Staphylococcus aureus

Streptococcus pneumoniae

LocusLink

CXCR4

MyD88

SwissProt

CAP18

CRAMP

IRAK4

TLR3

TLR4

TLR7

FURTHER INFORMATION

B. Brett Finlay's laboratory

Robert E. W. Hancock's laboratory

Functional pathogenomics of mucosal immunity

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