Table 1.
A. phagocytophilum strategies for intracellular survival and propagation, and their effect on histopathology and disease.
| A. phagocytophilum-related pathogetic mechanism | Target or effector molecule | Effect on A. phagocytophilum loada | Effect of gene deletion/pharmacologic/antibody inhibition on histopathologic lesionsb | References |
|---|---|---|---|---|
| Phagocyte oxidase | Disorganized assembly or transcriptional repression of host CYBB/RAC2 | 0 (in vivo); ↑↑↑ (in vitro) | ↓↓ (phox −/− B6 mice in vivo) | (Banerjee, et al., 2000, Banerjee, et al., 2000, Carlyon, et al., 2002, von Loewenich, et al., 2004, Scorpio, et al., 2006) |
| Chemokine/cytokine expression | IL8, IL-10:IFNγ | ↑↑ | 0 (CXCR1 antibody-treated vs. control antibody-treated in vivo); ↓↓ (in dexamethasone-treated horses) | (Akkoyunlu & Fikrig, 2000, Akkoyunlu, et al., 2001, Scorpio, et al., 2004, Davies, et al., in press) |
| A. phagocytophilum granulocyte entry |
A. phagocytophilum AnkA Host ROCK1 and Syk |
↑↑ to ↑↑↑ | ↓↓ to ↓↓↓ (vs. ROCK1 or Syk- silencing or vs. AnkA control antibody in vitro) | (Lin, et al., 2007, Thomas & Fikrig, 2007) |
| Histone deacetylase (HDAC) | HDAC1 and 2 | ↑↑ (vs. HDAC-silenced cells or NaB or trichostatin inhibition in vitro) | Not done | (Garcia-Garcia, et al., 2009) |
a
↑ - increased bacterial load or survival
b
↓ - decreased or “0” no change in histopathologic inflammation compared to unmodified control