Table 1.
The role of TLR activation in the pathogenesis of inflammatory diseases.
| Types of TLR | Associated diseases | Evidence | References |
|---|---|---|---|
| TLR2 | SLE | High mRNA expression in patients; TLR2−/− reduces autoantibody production | Komatsuda et al., 2008; Lartigue et al., 2009 |
| Sepsis | Up-regulated expression in patients; TLR2−/− increases survival under microbial infection | Harter et al., 2004; Bergt et al., 2013 | |
| Atherosclerosis | TLR2−/− decreases vasculature inflammation | Mullick et al., 2005, 2008 | |
| Hypertension | Renal IR injury | Khan et al., 2012 | |
| Psoriasis | Respond to HSP60 | Seung et al., 2007 | |
| COPD | Cigarette smoke-induced inflammation; exacerbation under infection | Droemann et al., 2005; Tokairin et al., 2008 | |
| TLR3 | Sepsis | TLR3−/− is protective against microbial challenge | Cavassani et al., 2008 |
| Atherosclerosis | Promote plague instability | Ishibashi et al., 2013 | |
| TLR4 | SLE | High mRNA expression in patients; TLR4−/− reduces autoantibody production; elevated TLR4 presents SLE-like phenotype | Liu et al., 2006; Komatsuda et al., 2008; Lartigue et al., 2009 |
| Sepsis | Up-regulated expression in patients; TLR4−/− is resistant to Gram-negative bacterial induced sepsis | Harter et al., 2004; Roger et al., 2009 | |
| Atherosclerosis | TLR4−/− decreases vasculature inflammation | Michelsen et al., 2004; Higashimori et al., 2011 | |
| Hypertension | Respond to angiotensin II | Hernanz et al., 2015 | |
| Psoriasis | Respond to HSP60 | Seung et al., 2007 | |
| IBD, gastrointestinal malignancies | Respond to resident microbes | Fukata et al., 2007; Fukata and Abreu, 2008 | |
| Asthma | Respond to airway allergens; Th1/Th2 immune homeostasis | Dong et al., 2009 | |
| COPD | Cigarette smoke-induced inflammation; exacerbation under infection | Karimi et al., 2006; Tokairin et al., 2008 | |
| TLR5 | Psoriasis | Respond to TGF-α | Miller et al., 2005 |
| TLR7 | SLE | Up-regulated expression in patients; TLR7−/− reduces autoantibody, IL-6 and IFN-α production | Christensen et al., 2006; Pisitkun et al., 2006; Subramanian et al., 2006; Lee et al., 2008; Kono et al., 2009 |
| Stroke | Dual role: protective in preconditioning, damaging in post-ischemia phase | Brea et al., 2011; Leung et al., 2012 | |
| Psoriasis | Aggravate disease symptoms | Gilliet et al., 2004 | |
| TLR9 | SLE | Regulatory role | Christensen et al., 2006; Nickerson et al., 2010; Chen et al., 2011; Jackson et al., 2014 |
| Sepsis | TLR9−/− is protective against microbial challenge; TLR9 inhibition reduces disease severity | Yasuda et al., 2008; Liu et al., 2012; Hu et al., 2015 | |
| Atherosclerosis | TLR9−/− exacerbates atherosclerosis | Koulis et al., 2014 | |
| Hypertension | Elevate blood pressure | McCarthy et al., 2015 | |
| Psoriasis | Respond to TGF-α | Miller et al., 2005 | |
| COPD | Cigarette smoke-induced inflammation | Mortaz et al., 2010 |
SLE, systemic lupus erythematosus; IR, ischemia-reperfusion; HSP, heat shock protein; COPD, chronic obstructive pulmonary disease; IBD, inflammatory bowel diseases.