Table 3.
Leptospira-induced apoptosis and cell death.
| Leptospira spp | Host cells | Main findings | Technical remarks | Ref |
|---|---|---|---|---|
| L. interrogans Icterohaemorrhagiae | Vero and J774A.1 cell lines | Live pathogenic leptospires induced DNA fragmentation in Mφ. The saprophytic and avirulent strain did not induce DNA fragmentation. |
No gentamicin protection assay Noninfected controls missing |
(18) |
|
L. interrogans Lai, Luo L. biflexa Patoc |
Vero and J774A.1 cell lines | Subcellular “lesions” upon infection with Lai (virulent) and Luo (avirulent) (EM). Surprisingly, Lai was occasionally associated with nuclei. Live and UV-killed Lai and Luo induced apoptosis (annexin V+/PI-) in Vero cells and necroptosis (annexin V+/PI+) in Mφ. Both live and UV-killed serovars produced a similar phenotype. |
No gentamicin protection assay Noninfected controls missing |
(23) |
|
L. interrogans Lai L. biflexa Patoc |
BALB/c naive peritoneal Mφ J774A.1, A549, HUVEC, and ECV304 cell lines |
Infection of Mφ and A549 cells induced cell death (LDH release-, MOI- and time-dependent) Lai (virulent) but not Patoc induced apoptosis (2–6 hpi) and later induced (> 12 hpi) necroptosis. Caspase-3, -6, -8, and -9 were activated upon infection with Lai but not with Patoc. Lai induced cleavage of PARP and Lamin A/C. FADD levels increased upon infection of Mφ. Induction of apoptosis was also observed in primary naive peritoneal Mφ. |
No gentamicin protection assay Noninfected controls missing |
(27) |
| L. interrogans Lai, Pomona Luo (avirulent) | Human (THP-1 and primary Mφ) and murine (J77A.1 and peritoneal BALB/c Mφ |
Lai (virulent) induced increased apoptosis in murine Mφ compared to that in human Mφ (0–24 hpi). Lai induced necroptosis in murine Mφ (8–48 hpi). |
No gentamicin protection assay | (20) |
|
L. interrogans Manilae L. biflexa Patoc |
C57BL/6 BMMs |
No cell death was associated (no LDH release) with L. interrogans or L. biflexa infection. | Positive control for LDH release | (24) |
| L. interrogans Lai | THP-1 and J774.1 cell lines | Infection triggered accumulation of p53 and H2AX foci in a ROS-dependent manner. Leptospire infection arrested the cell cycle. Apoptosis/necrosis induced upon infection of Mφ. |
(21) | |
| L. interrogans Pomona | Bovine PBMCs | Infection triggered the formation of bMETs independently of the virulence of leptospires. | (26) |
Mφ, macrophages; EM, electron microscopy; PI, propidium iodine; UV, ultraviolet; ND, nondescribed; pi, postinfection; ROS, reactive oxygen species; IP3, inositol-3-phosphate; bMETs, bovine macrophage extracellular traps; ⪼.
Host cells: THP-1, human monocyte cell line; J774.1, murine macrophage-like cell line; BMMs, bone marrow-derived macrophages; Vero, monkey kidney epithelial cells; PBMCs, peripheral blood mononuclear cells; A549, adenocarcinomic human alveolar basal epithelial cells; HUVECs, human umbilical endothelial cells; ECV340, human bladder epithelial cells; PMNs, polymorphonuclear cells. In red and green, technical remarks that mitigate or confirm the authors’ findings.