Table 1.
The role of TIM3 in infectious diseases.
| Disease model | Cell types | Ligand | Interact with | Infection phase | Subject | Function of TIM3 | Ref. |
|---|---|---|---|---|---|---|---|
| M. Tuberculosis (Mtb) | CD8+T | Galectin-9 | Macrophage | Chronic | Murine | triggers IL-1β production by macrophages and limits intracellular Mtb replication. restrains TIM3+ effector T cell responses. |
(54) |
| CD8+T | Galectin-9 | Macrophage | Chronic | Murine | co-express with other inhibitory receptors, marking the subset of effector T cell that is functionally exhausted. TIM3 blockade restores T cell function and improves bacterial control. |
(58) | |
| CD4+T CD8+ T |
– | Macrophage | Chronic | Human | limits intracellular Mtb replication TIM3+T-cell subsets express much higher levels of phosphorylated signaling molecules (p38, stat3, stat5, and Erk1/2) |
(56) | |
| HIV | CD8+T | – | – | Chronic | Human | TIM3 levels are positively correlated with viral load and disease progression marks the dysfunctional subset of CD8+ T cells in HIV patients TIM3 blockade can restore the proliferative response of TIM3+ CD8+ T cells to HIV-1 peptides in vitro |
(48) |
| CD4+T | Galectin-9 | – | – | Human | lowers the expression of the HIV co-receptors CCR5, CXCR4 and α4β7 on the T cells, thus enabling resistance to HIV infection. | (70) | |
| HCV | CD4+T CD8+T |
– | – | Chronic | Human | marks dysfunctional T cell population TIM3 blockade can restore the T cell response to HCV infection by enhancing T-cell proliferation and gamma interferon production |
(45, 46) |
| HBV | CD4+T CD8+T |
Galectin-9 | Kupffer cell | Acute and Chronic | Human | marks the dysfunctional T cell population Tim-3 blockade results in enhanced expansion of HBV-specific CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. |
(71) |
| CD4+T CD8+T |
– | – | Chronic | Human | over-expression of Tim-3 is involved in disease progression of hepatis B and contributes to persistency of infection | (47) | |
| Listeria monocytogenes | Macrophage | – | – | Chronic | Murine | dampens macrophage phagocytosis by inhibiting the Nrf2-CD36/HO-1 signaling pathways. increases bacterial burden/infection tolerance during chronic infection. |
(72) |
| CD8+T | Acute | Murine | enhances CD8 T cell responses to acute Listeria monocytogenes infection. | (53) | |||
| HSV-1 | CD8+T | Galectin-9 | Neuronal cells | Chronic/latent | Murine | Galectin-9/Tim-3 interaction is responsible for reduced CD8+ T cell effector function. | (73) |
| LCMV | CD8+T | – | – | Chronic | Murine | Co-expression of Tim-3 and PD-1 is associated with more severe CD8 T-cell exhaustion | (49) |
Nrf2, nuclear factor erythroid 2 related factor; HO-1, heme oxygenase-1; HSV-1, herpes simplex virus-1; LCMV, lymphocytic choriomeningitis virus.