Innate immunity in host-microbial interactions: Beyond B27 in the spondyloarthropathies

Abstract

The spondyloarthropathies are diseases influenced by genetic predisposition and, to a varying extent, infectious triggers. A causal role for bacterial infections is most clear for reactive arthritis. Recent insights into arthritogenic components of bacteria may set the stage for a better understanding of disease pathogenesis, the role of heat shock proteins in antigen processing and immune activation, and the adjuvant effect of CpG-DNA. Recent developments in the area of innate immunity broaden current concepts of genetically defined factors in host-pathogen interactions. In particular, the biology of toll-like receptors as important elements in the innate immune response to pathogens is being defined. These factors in innate immunity may have important implications for sequelae of infections, such as reactive arthritis.

Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity

“…The pathophysiology of these diseases is not completely understood, but it is believed that the genetic component is directly involved as demonstrated by transgenic rats expressing human HLA-B27 [ 2 ]. Environmental factors also play a role in SpA, particularly bacterial antigens from the gut or the genitourinary tract [ 3 ]. Different cellular subsets are observed in the joints or entheseal structures of SpA including macrophages and neutrophils, and also CD8+ and CD4+ T lymphocytes [ 4 , 5 ].…”

Aberrant TNF secretion by whole blood in healthy subjects with a history of reactive arthritis: time course in adherent and non-adherent cultures

“…1 The pathogenesis of reactive arthritis is unclear but may involve aberrations in the adaptive immune response-for instance, presentation of arthritogenic self peptides to CD8 + T cells by HLA-B27, or formation of HLA-B27 dimers recognised by CD4 + T cells. 2 However, evidence has accumulated to show that innate immune reactions, which represent early stages of the host defence against the arthritogenic microbes, 3 may also play a role in the development of reactive arthritis. Innate immune system receptors, such as CD14/Toll-like receptor complexes on monocytes and macrophages, recognise lipopolysaccharides (LPS) and other pathogen associated molecular patterns.…”

Microbe hunting in the joints

“…1) The recently discovered receptors of the first line of host defense-the Tolllike receptors (TLR)-recognize a range of microbes and their products. For example, TLR2 recognizes bacterial peptidoglycan (10). 2) Bacterial peptidoglycan is capable of stimulating synovial macrophages to express the costimulatory molecules CD80 and CD86, and to produce proinflammatory cytokines such as tumor necrosis factor ␣ and interleukin 6 (11).…”