Table 1 |.
Characteristics of mouse models of lyme arthritis
| Mouse model | Immune defect | Effect on arthritis | Effect on host defence | Relevance to human disease | Refs |
|---|---|---|---|---|---|
| C57BL/6 (B6) | NA | Mild, self-resolving Lyme arthritis | NA | Probably mimics patients who develop only mild Lyme arthritis | 20 |
| C3H/HeN (C3H) | NA | Severe, acute, self-resolving Lyme arthritis | NA | Most similar to severe Lyme arthritis during active infection | 20 |
| Il10−/− (B6) | Dysregulated NF-κB and TH1 cell responses; impaired regulatory T cells | More severe (increased innate and adaptive inflammation) | Very few Borrelia burgdorferi in joints compared with B6 or C3H mice | Mimics dysregulated TH1 cell responses seen in patients who develop post-infectious Lyme arthritis9,10,43,70,71 | 101,109,110 |
| Tlr1−/− or Tlr2−/− (B6 or C3H) | Impaired response to Borrelia lipoproteins (such as OspA and OspC) | More severe (probably owing to impaired host defence) | ~100-foid more B. burgdorferi in joints compared with wild-type mice; OspA vaccine non-protective | Low TLR1 in vaccine low responders75; TLR1 hypomorph associated with severe Lyme arthritis41 | 74,75 |
| Mir146a−/− (B6) | Hyperactive NF-κB signalling | More severe (increased acute inflammation) | Slightly fewer B. burgdorferi in joints compared with wild-type mice | Probably reflects the central importance of NF-κB regulation in host defence and arthritis during infection9 | 100 |
| Ifnar−/− (C3H) | Defect in type I interferon signalling | Less severe (type I interferon is arthritogenic) | No effect | Unclear, might be important in early infection of skin | 59 |
| C3H Gusb allele (B6) | B6 mice with C3H Gusb allele are unable to clear ECM debris | More severe (accumulated glycosaminoglycans in joints) | No effect | Unclear, might be important in clearing B. burgdorferi peptidoglycan and host ECM debris | 77 |
ECM, extracellular matrix; NA, not applicable; Osp, outer-surface protein; TH1 cell, T helper 1 cell; TLR1, Toll-like receptor 1.