Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols

Abstract

BackgroundThe inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum.MethodsForty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA analysis during infection. Blood was also collected for the determination of IL-1β concentration.ResultsRabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1β secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to “normal” levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1β mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1β expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1β in the testes of the infected rabbits.ConclusionsThis study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages

“…10 Treponema pallidum-induced activation of the NLRP3 inflammasome led to elevated levels of pro-inflammatory cytokines and was closely linked to the development and progression of syphilitic inflammation. 2 Prior studies have noted that activation of the NLRP3 inflammasome modulates autophagy to enhance intracellular clearance of mycobacteria. 21 The results of our study also showed that transfected siRNA targeting NLRP3 reduced the level of autophagy and attenuated macrophage phagocytosis.…”

“…Our previous studies found that T. pallidum induced the NLRP3 inflammasome in a dose-and time-dependent manner. 2,10 Since autophagy has been identified as an efficient means for host cells to eradicate intracellular pathogens, we next evaluated the role of the NLRP3 inflammasome in modulating the autophagic response in T. pallidum-infected macrophages. Real-time PCR showed that the relative mRNA levels of NLRP3, caspase-1, Beclin-1 and LC3B in the si-NLRP3 group were 43.04%, 37.63%, 49.86% and 43.02%, respectively, ( Fig.…”

“…1 Our previous studies showed that macrophages comprise the first line of the host innate immune response and play a crucial role during early syphilis. 2,3 Macrophages have been reported to participate in the eradication of treponemes primarily through phagocytosis of spirochetes. 4 Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against T. pallidum.…”

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1β production

“…Syphilis is an infectious, sexually transmitted disease resulting from infection by Treponema pallidum [ 1 , 2 ]. Develop lesions in compromised tissues of infected patients are a direct manifestation of the inflammatory processes triggered by T. pallidum [ 2 – 4 ]. T.pallidum ’ pathogen-associated molecular patterns are recognized by the host immune system through pattern recognition receptors expressed by macrophages or dendritic cells, including intracellular receptors and membrane-bound [ 4 – 6 ].…”

“…Develop lesions in compromised tissues of infected patients are a direct manifestation of the inflammatory processes triggered by T. pallidum [ 2 – 4 ]. T.pallidum ’ pathogen-associated molecular patterns are recognized by the host immune system through pattern recognition receptors expressed by macrophages or dendritic cells, including intracellular receptors and membrane-bound [ 4 – 6 ]. This recognition of pathogen-associated molecular patterns activates various members of the nucleotide-binding leucine-rich receptor (NLR) family in the cytoplasm, which results in the assembly of an NLR-containing multiprotein complex that recruits and activates caspase-1 and thereby in the production of proinflammatory cytokines, including interleukin (IL)-1β, IL-18 and IL-33.…”