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. 2018 Mar 1;18(1):101.
doi: 10.1186/s12879-018-2993-0.

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

Li-Rong Lin  1   2 , Yao Xiao  1   3 , Wei Liu  1   2 , Yu-Yan Chen  4 , Xiao-Zhen Zhu  1   2 , Zheng-Xiang Gao  1   2 , Kun Gao  1   2 , Man-Li Tong  1   2 , Hui-Lin Zhang  1   2 , Shu-Lian Li  5 , Hui-Ling Lin  5 , Wen-Dong Li  5 , Xian-Ming Liang  1 , Yong Lin  6   7 , Li-Li Liu  8   9 , Tian-Ci Yang  10   11
Affiliations

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

Li-Rong Lin et al. BMC Infect Dis. .

Abstract

Background: The 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.

Methods: Forty-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.

Results: Rabbits 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.

Conclusions: This 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.

Keywords: Il-1β; Inflammation; NLRP3; Rabbit; Treponema pallidum.

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Conflict of interest statement

Ethics approval

This study was approved by the animal experimental ethics committee of the Medical College of Xiamen University.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Dynamics of the cutaneous lesion size in rabbits infected with T. pallidum. a Lesions of one representative rabbit in the BPG treatment subgroup at 16 d. b Lesions of one representative rabbit in the no BPG treatment subgroup at 18 d. c Dynamics of the cutaneous lesion size in rabbits infected with T. pallidum. The arrow shows the time point of BPG treatment. The results are expressed as the mean ± SD. Student’s t-test was applied to compare the means of the diameters between the BPG treatment and no BPG treatment subgroups. *P < 0.05
Fig. 2
Fig. 2
Dynamics of NLRP3, caspase-1, and IL-1β mRNA expression in cutaneous lesions in rabbits infected with T. pallidum. a Dynamics of NLRP3 mRNA in cutaneous lesions in rabbits infected with T. pallidum. b Dynamics of caspase-1 mRNA in cutaneous lesions in rabbits infected with T. pallidum. c Dynamics of IL-1β mRNA in cutaneous lesions in rabbits infected with T. pallidum. The arrow shows the time point of BPG treatment. Values represent the mean ± SD of triplicate experiments. A one-way analysis of variance was employed to examine the differences in the three groups, and Dunnett’s post-comparison test was used to conduct multiple comparisons. * P < 0.05, the BPG treatment subgroup or no BPG treatment subgroup vs. the blank group. # P < 0.05, the BPG treatment subgroup vs. the no BPG treatment subgroup
Fig. 3
Fig. 3
Dynamics of the IL-1β concentration in rabbits infected with T. pallidum. Values represent the mean ± SD of triplicate experiments. A one-way analysis of variance was employed to examine the differences between groups, and Dunnett’s post-comparison test was used to conduct multiple comparisons. * P < 0.05, the BPG treatment subgroup or no BPG treatment subgroup vs. the blank group
Fig. 4
Fig. 4
Dynamics of NLRP3, caspase-1, and IL-1β mRNA expression in organs of rabbits infected with T. pallidum. a-e Dynamics of NLRP3 mRNA expression in the kidney (a), liver (b), lung (c), spleen (d) and testis (e). f-j Dynamics of caspase-1 mRNA expression in the kidney (f), liver (g), lung (h), spleen (i) and testis (j). k-o Dynamics of IL-1β mRNA expression in the kidney (k), liver (l), lung (m), spleen (n) and testis (o). Values represent the mean ± SD of triplicate experiments. A one-way analysis of variance was employed to examine the differences in groups, and Dunnett’s post-comparison test was used to conduct multiple comparisons. * P < 0.05, the BPG treatment subgroup or no BPG treatment subgroup vs. the blank group
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