Table 1.
Immunoregulatory effects of major known spirochetal lipoproteins.
| Spirochetal lipoproteins | Endothelial cells | Neutrophils | Complement | Antigen presenting cells: monocytes/macrophages/DCs | Lymphocytes |
|---|---|---|---|---|---|
| Treponema pallidum: mixture of bacterial lipoproteins of various MW [17 kDA (33), 38 kDA (34), 47 kDA (35)] and related synthetic lipopeptides (22, 30) | Activate directly host vascular endothelium which plays important roles in lymphocyte homing and hemostasis (36) | NR | NR | Stimulate macrophage and mDCs function: costimulatory signals (DC-SIGN, CD14) (11, 37, 38) and production of chemokines (CCR5) (39, 40), cytokines such as TNF-a, IL-1 beta, IL-6, and IL-12 (18, 33, 35, 41) through TLRs (42) and mostly TLR2 (43), activated IL-12 p40 promoter (42), NF-KB pathway (37, 38) | Up-regulate CCR5 expression on CD4+ T cells (39, 40) |
| Borrelia burgdorferi: outer-surface protein A (OspA) and B (OspB) and related synthetic lipopeptides (20, 44–46) | NR | OspB inhibits the phagocytosis and oxidative burst of human neutrophils whereas OspA induces the oxidative burst in neutrophils (47) | Deactivation of host complement by binding to CFH and FHL-1 (47–49) | Stimulate macrophage function and production of nitric oxide (42, 50), chemokines (CXCL13) (51), pro-inflammatory (such as TNF-a, IL-1 beta, IL-6, and IL-12) and anti-inflammatory (IL-10) cytokines (18, 35, 41, 44, 52–55) through TLRs (28, 42, 44, 45, 56, 57), CD14, and NF-kB activation pathway (37, 38, 44, 45). Also increase chemotaxis of circulating pDCs into skin (11) but do not activate pDCs in vitro and in vivo (58, 59) | Induce memory B cell immune responses (60), B cell proliferation and production of cytokines (61) and Th production of cytokines (IFN-γ and IL-6) (62) and chemokines (CXCL13) (51). OspA may bind TLR 2 and 6, activate NFκB and up-regulate costimulatory molecules as well as of MHC class II, leading to stronger T cell activation (63–65); Possible molecular mimicry for T helper cells between OspA-1 and LFA-1 (66–68). OspA-1 may activate autoreactive T cells against a self-epitope and adaptive immune responses to OspA are implicated in the pathogenesis of antibiotic- refractory Lyme arthritis (68, 69) |
| Leptospira interrogans LipL32 is the most abundant protein on the outer membrane of Leptospira and is expressed at high levels during infection (2, 70–76) | LipL32 interacts with endothelial cells contributing to systemic inflammation (77–80) | NR | NR | The calcium-binding cluster is crucial for the interaction between LipL32 and TLR2, which then triggers the signaling cascade of inflammatory responses (56, 72, 81) | Lipl32 has been used as immunogen for vaccine trials (82, 83) |
CFH, complement factor H; FHL-1, factor H-like protein 1; IL, interleukin; kDA, kilodalton; LipL32, 32-kDa lipoprotein of Leptospira; LFA-1, human lymphocyte function associated antigen 1; mDCs, myeloid dendritic cells; MW, molecular weight; NF-kB, NF-kappa B; NR, not reported; OspA, outer-surface protein A; OspB, outer-surface protein B; pDCs, plasmacytoid dendritic cells; TLR, toll-like receptor; Th, T helper; TNF-a, tumor necrosis factor.