Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats

Abstract

SUMMARYStreptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis that can be induced in susceptible Lewis rats by one i,p, injection of an aqueous, sterile suspension of SCW, F344 rats are resistant to chronic joint inflammation. Our previous studies showed a correlation between susceptibility to SCW-induced arthritis and the ability to mount SCW-specific T cell responses, suggesting tolerance to SCW as a putative mechanism. Here we prevented the induction of tolerance to bacterial epitopes in F344 rats by using them germ-free and analysed susceptibility to arthritis subsequently. In addition, we conventionalized germ-free F344 rats at different times before induction of arthritis. Our results show that germ-free F344 rats are susceptible to SCW-induced arthritis with a similar severity, chronicity, incidence and onset as Lewis rats. Moreover, T cells isolated from germ-free F344 rats were able to respond to SCW, Conventionalization dramatically moderates arthritis and makes T cells unresponsive to SCW again. Thus, in normal rats (F344) a state of tolerance to arthritogenic epitopes is induced (neonatally) and maintained through life by the bacterial flora, resulting in resistance to bacterium-induced artritides. In arthritis-prone (Lewis) rats, this tolerance is deficient and/or easily broken.

The microbiome and rheumatoid arthritis

“…In this model, animals reared conventionally are resistant to joint inflammation, whereas germ-free rats become susceptible to arthritic disease, mainly through loss of T-cell tolerance. 74 These findings support the concept that gut and joint inflammation are interconnected through the part played by the commensal gut flora in immune homeostasis. Whether flora is protective or deleterious for joint health might also be related to the host genetic background, as differing experimental results described above were conducted using alternate rat strains with various degrees of arthritis susceptibility.…”

Review: Microbiome in Inflammatory Arthritis and Human Rheumatic Diseases

“…Furthermore, bacteria‐derived lipopolysaccharide by itself is also capable of potentiating CIA in mice . Similarly, in the streptococcal cell wall–induced arthritis model in rats, the presence of gut microbiota renders animals resistant to joint inflammation .…”

Probiotics and immunity: provisional role for personalized diets and disease prevention

“…Recently, the has also been observed the growing body of evidence linking the microbiome with rheumatoid arthritis (RA) pathogenesis [ 67 – 69 ], however, still far from a novel concept [ 70 ].…”