Table 1.
Mtb virulence factors counteracting the innate immune response
| Mtb effectors | Action | Mechanism | Cell type | References |
|---|---|---|---|---|
| Intracellular trafficking and localization | ||||
| ESAT‐6 | Translocation into the cytosol | ESAT‐6 has a pore forming activity | THP‐1, DCs | van der Wel et al., 2007; Houben et al., 2012; Simeone et al., 2012 |
| LAM | Inhibits phagolysosome fusion | Unknown | THP‐1/MDMs | Hmama et al., 2004; Kang et al., 2005; Welin et al., 2008 |
| PtpA | Inhibits phagosome acidification | vATPase exclusion | THP‐1 | Bach et al., 2008; Wong et al., 2011; Wong and Jacobs, 2011 |
| Autophagy | ||||
| ESAT‐6 | Inhibits production of IFN‐γ | Affects TCR signalling | T cells | Wang et al., 2009 |
| ESX‐1 secretion system | Inhibition of autophagosomes/lysosome fusion | Unknown | DCs | Romagnoli et al., 2012 |
| LAM | Blocks transcriptional activation of IFN‐γ | Unknown | U937/THP‐1 | Chan et al., 1991 |
| miR‐30A | Inhibition of autophagy | Unknown | THP‐1 | Chen et al., 2015 |
| Sulfatide | Blocks IFN‐γ or lipopolysaccharide priming | Unknown | Monocytes | Pabst et al., 1988 |
| Host cell death | ||||
| ESAT‐6 | Induces necrotic death | Caspase‐1‐ and cathepsin B‐independent necrosis | MDMs | Welin et al., 2011 |
| ESX‐1 secretion system | Extracellular traps | Unknown | MDMs | Wong and Jacobs, 2013 |
| CpnT | Induces necrotic death | Unknown | Jurkat T | Danilchanka et al., 2014 |
| SecA2 and NuoG | Suppress apoptosis | Unknown | THP‐1 | Hinchey et al., 2007; Velmurugan et al., 2007; Miller et al., 2010 |
| PknE | Inhibits apoptosis | Unknown | THP‐1 | Jayakumar et al., 2008 |
| Rv3364c | Suppresses caspase‐1 and pyroptosis | Inhibition of cathepsin G activity | U937 | Danelishvili et al., 2011 |
| Reactive species and toxic metals | ||||
| Eis | Modulates ROS production | Targets JNK pathway | THP‐1 | Shin et al., 2010 |
| ctpC | Zinc detoxification | Zinc efflux | MDMs | Botella et al., 2011 |
| NuoG | Neutralizes ROS and TNF‐α‐mediated host cell apoptosis | Unknown | AMs | Miller et al., 2010 |
Mtb effector abbreviations: CpnT, C‐terminal domain of the channel protein with necrosis‐inducing toxin; Eis, enhanced intracellular survival protein; LAM, lipoarabinomannan; PknE, protein kinase E; PtpA, tyrosine phosphatase. Cell type abbreviations: AMs, alveolar macrophages; DCs, dendritic cells; MDMs, monocyte‐derived macrophages.