Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella

Abstract

Holzapfel et al. TLR5 Evasion by Leptospires the FlaB, but not the FlaA subunits. Altogether, in contrast to different bacteria that modify their flagellin sequences to escape TLR5 recognition, our study suggests that the peculiar central localization and stability of the FlaB monomers in the periplasmic endoflagellae, associated with the downregulation of FlaB subunits in hosts, constitute an efficient strategy of leptospires to escape the TLR5 recognition and the induced immune response.

Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

“…However, although the Icterohaemorrhagiae Verdun strain is pathogenic [ 66 , 67 ], and like other serovars may cause pulmonary hemorrhages, a syndrome also frequently described in guinea pigs, and reported associated with the most severe human leptospirosis cases [ 68 ], it has also been reported that experimental infection with Icterohaemorrhagiae strains in outbred mice and hamsters results in subclinical infections [ 67 ]. Host-species differences of Leptospira innate sensing have already been described between mice and humans [ 69 – 71 ], but potential differences between rats and mice have not yet been investigated. It would be interesting to use a more mouse-adapted serovar such as Arborea or Australis [ 72 ] and repeat these experiments to test whether these leptospires colonize the mouse kidneys and also elicit sustained IgM.…”

“…Alternatively, this may suggest that the IgA response could be specific to the Fiocruz pathophysiology. Interestingly we recently showed that live leptospires (Manilae L495, Copenhageni Fiocruz L1-130 and Icterohaemorrhagiae Verdun Cl3) escape the TLR5 recognition in vivo in mice and in vitro in human cells [ 71 ]. However, once heat-killed or degraded by antimicrobial peptides, only the Copenhageni strain was able to signal through mouse-TLR5 [ 71 ].…”

“…Interestingly we recently showed that live leptospires (Manilae L495, Copenhageni Fiocruz L1-130 and Icterohaemorrhagiae Verdun Cl3) escape the TLR5 recognition in vivo in mice and in vitro in human cells [ 71 ]. However, once heat-killed or degraded by antimicrobial peptides, only the Copenhageni strain was able to signal through mouse-TLR5 [ 71 ]. Mouse-TLR5 activation has been associated with anti-flagellin IgA secretion [ 90 ].…”

Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

“…However, although the Icterohaemorrhagiae Verdun strain is pathogenic (63, 64), and like other serovars may cause pulmonary hemorrhages, a syndrome also frequently described in guinea pigs, and reported associated with the most severe human leptospirosis cases (65), it has also been reported that experimental infection with Icterohaemorrhagiae strains in outbred mice and hamsters results in subclinical infections (64). Host-species differences of Leptospira innate sensing have already been described between mice and humans (66–68), but potential differences between rats and mice have not yet been investigated. It would be interesting to use a more mouse-adapted serovar such as Arborea or Australis (69) and repeat these experiments to test whether these leptospires colonize the mouse kidneys and also elicit sustained IgM.…”

“…Alternatively, this may suggest that the IgA response could be specific to the Fiocruz pathophysiology. Interestingly we recently showed that live leptospires (Manilae L495, Copenhageni Fiocruz L1-130 and Icterohaemorrhagiae Verdun Cl3) escape the TLR5 recognition in vivo in mice and in vitro in human cells (68). However, once heat-killed or degraded by antimicrobial peptides, only the Copenhageni strain was able to signal through mouse-TLR5 (68).…”