Innate immune responses to commensal bacteria in inflammatory bowel disease

Crohn's disease and ulcerative colitis are the two major forms of IBD characterized by acute and chronic inflammation in the absence of a known pathogen. These inflammatory disorders are distinguished by the depth and location of inflammation with ulcerative colitis being limited to the mucosa of the colon and Crohn's disease involving both the small intestine and the colon in a transmural fashion. The patho-genesis of Crohn's disease and ulcerative colitis is multifactorial, resulting from the...

TLR polymorphisms and association studies of allergic disease

Given the opposing effects of endotoxin, it is perhaps not unexpected that some studies have not revealed an effect of the common TLR4 polymorphism (D299G) on the overall incidence of asthma 116-118 . Individuals having this polymorphism have a blunted airway response 21 and reduced systemic inflammation 119 in response to inhaled endotoxin. Consistent with these observations, a study of asthma specifically associated with endotoxin in house dust showed that people with the TLR4 polymorphism...

Conclusion

Multiple lines of investigation have revealed the importance of TLRs in the development and progression of asthma. By signaling in response to inhaled pathogens or endogenous ligands, TLRs regulate both innate and adaptive immune responses Mechanisms associated with TLR-dependent regulation of inflammation TLR receptors are expressed on both antigen presenting cells as well as T-regulatory cells. Activation of TLRs can result in production of both proinflammatory or anti-inflammatory cytokines,...

Exogenous TLR ligands implicated in the progression of atherosclerosis

A number of infectious agents have been associated with atherosclerotic cardiovascular disorders, including Chlamydia pneumoniae 47 , Helicobacter pylori 48 , cytomegalovirus (CMV) 49 , Epstein-Barr virus 50 , human immunodeficiency virus 51 , herpes simplex viruses (HSV)1 52 , HSV2 53 , and hepatitis B 54 and C 55 . More recent models emphasize the relationship of atherosclerosis to total infectious burden rather than specific pathogens 56 . The above mentioned infectious agents or derived...

Endogenous TLR ligands and products of tissue destruction

It is now recognised that in addition to binding PAMPs, TLR's can also recognise endogenous signals released from injured tissue and cells undergoing necrotic cell death, such as HSP60. There are already examples of endogenous molecules signalling through TLR2, TLR3, TLR4 and TLR9. HSPs are recognised by TLR2 and TLR4, in particular HSP60 69 , HSP70 70 and gp96 71 , which are released by cells undergoing necrosis. HSP-peptide complexes are able to elicit peptide specific CD8+ T cell responses...

List of contributors

Abreu, Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA e-mail maria.abreu mssm.edu Moshe Arditi, Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 4220, Los Angeles, CA 90048, USA e-mail moshe.arditi cshs.org Tamas Bartfai, Department of Neuropharmacology, The Harold L. Dorris Neurological Research...

TLR ligands during allergic sensitization

On the surface, findings related to the actions of TLRs in allergic asthma appear highly contradictory as endotoxin has been reported to both exacerbate asthma and diminish its incidence. Multiple epidemiologic studies have shown that exposure to TLR ligands in childhood is protective against developing asthma later in life. Examples of this include individuals living on farms who have a reduced risk of developing hay fever or asthma 66-68 , the inverse relationship shown between prior measles...

Targeting TLRs with specific ligands

Several synthetic TLRs ligands are available. Most of them are specific for one TLR and are being tested in different applications (Fig. 2). Novel therapeutic vaccinations are being developed to activate tumor antigen-specific T cells and prolong their activity in the host. Adjuvants based on dsRNA directly stimulate TLR3, present on myeloid dendritic cells and T cells in humans 28 . Poly I C was the first dsRNA to be used clinically in leukemia and HIV patients for its ability to stimulate...