Bacterial infections in Wegener's granulomatosis: mechanisms potentially involved in autoimmune pathogenesis.

Abstract

PURPOSE OF REVIEW:

Wegener's granulomatosis is associated with bacterial infection, in particular nasal carriage of Staphylococcus aureus. Infection may play a role in the induction of autoimmunity as well as in the effector phase of the disease. Here, the current hypotheses aiming to explain the link between infections and Wegener's granulomatosis immunopathogenesis are reviewed and discussed.

RECENT FINDINGS:

In recent years, studies suggested that molecular mimicry could play a role in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), either via direct mimicry between human lysosome-associated membrane protein-2 and bacterial FimH or indirectly via the development of antibodies against a peptide complementary to proteinase 3 (cPr3). More recent work has focused on Toll-like receptors (TLRs), a family of receptors specialized in the recognition of pathogen-associated molecular patterns. In animal models, it has been shown that TLR ligands can aggravate anti-MPO antibody-mediated disease. Furthermore, it was shown that a TLR9 ligand can trigger the production of ANCA in vitro by peripheral blood-derived B lymphocytes from AAV patients. The newly described process of ANCA-mediated neutrophil extracellular trap formation may provide an endogenous TLR9 ligand. Finally, TLR2 signaling is involved in the development of a Th17-driven immune response, consistent with skewing towards a Th17 T cell phenotype that has been observed in Wegener's granulomatosis.

SUMMARY:

Although Wegener's granulomatosis pathophysiology is becoming better understood, the specific events leading to autoimmunity are not clear. Recent studies show that several mechanisms may be involved in linking infection to autoimmunity. Molecular mimicry may be involved, and a role for TLR signaling is suggested.

• Authors: Henko Tadema, Peter Heeringa, Cees G M Kallenberg
• Journal: Current opinion in rheumatology (Curr Opin Rheumatol) Vol. 23 Issue 4 Pg. 366-71 (Jul 2011) ISSN: 1531-6963 [Electronic] United States
• PMID: 21494184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Toll-Like Receptors

Topics

• Bacterial Infections (complications, immunology, microbiology)
• Granulomatosis with Polyangiitis (etiology, immunology, microbiology)
• Humans
• Signal Transduction (immunology)
• Toll-Like Receptors (physiology)