Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study

Pastuszczak, Maciej; Goździalska, Anna; Jakieła, Bogdan; Obtułowicz, Aleksander; Jaśkiewicz, Jerzy; Wojas‐Pelc, Anna

doi:10.1136/sextrans-2016-052681

Cited by 29 publications

(22 citation statements)

References 19 publications

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“…A diagnosis of syphilis in humans and animal models is typically characterized by elevations in both plasma pro-inflammatory (TNFα, IFNγ, CCL4, IP-10) and anti-inflammatory cytokines (IL-10) [ 11 – 18 ]. This immunological profile however varies according to a number of parameters including stage of syphilis [ 4 , 17 – 20 ], HIV-infection status [ 20 ] and the number of previous episodes of syphilis [ 4 , 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

et al. 2018

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BackgroundAscertaining if the clinical and immunological response to repeat syphilis differs from that in initial syphilis may assist in designing optimal syphilis screening strategies and vaccine design.MethodsWe prospectively recruited 120 patients with a new diagnosis of (baseline) syphilis. During a 24-month follow-up period, 11 of these patients had a further diagnosis of (repeat) syphilis. We conducted a paired comparison of their plasma cyto-chemokines at baseline and repeat syphilis.ResultsComparing to their baseline infection, paired analyses of the 11 individuals with repeat infections during follow-up revealed that these reinfections had lower concentrations of Interferon (IFN)α (0.8 [Interquartile range (IQR) 0.8–0.8 vs. 12.2 [IQR 1.6–24.2], P = 0.004) and Chemokine (C-C motif) ligand (CCL) 4 (0.9 [IQR 0.9–12.2 vs. 17.5 [IQR 4.9–32.8], P = 0.022].ConclusionIn this small study of 11 individuals, repeat syphilis was found to present with an attenuated immune response. The relevance of these findings to the design of optimal syphilis screening programs is discussed.

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Section: Discussionmentioning

confidence: 99%

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

et al. 2018

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“…After treatment, titres generally decline and in most immunocompetent individuals become nonreactive within 6 months. However, up to 20% of syphilis-infected individuals have a persistently reactive (albeit low-titre) NTT even after treatment, possibly related to a less robust pro-inflammatory immune response 135 . These patients are labelled as having a serofast status and are observed more commonly with treatment for late latent than early syphilis 37,136 .…”

Section: Diagnosis Screening and Preventionmentioning

confidence: 99%

Syphilis

Peeling

Mabey

Kamb

et al. 2017

Nat Rev Dis Primers

519

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Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochetes and often imitate those of other diseases. The spirochete has a long latent period during which patients have no signs or symptoms, but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries. Syphilis also causes several hundred thousand stillbirths and neonatal deaths every year in developing nations. Although several low-income countries have achieved WHO targets for the elimination of congenital syphilis, an alarming increase of syphilis in HIV-infected MSM serves as a strong reminder of the tenacity of T. pallidum as a pathogen. Strong advocacy and community involvement is needed to ensure that syphilis is given high priority on the global health agenda. More investment in research is needed on the interaction between HIV and syphilis in MSM, as well as into improved diagnostics, a better test of cure, intensified public health measures and, ultimately, a vaccine.

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“…10 A robust pro-inflammatory response may facilitate the clearance of T. pallidum. 11 Numerous studies have revealed the role of the inflammasome in regulating autophagy. 12,13 However, whether the NLRP3 inflammasome, which could mediate pro-inflammatory cytokine release, plays a regulatory mechanism in autophagy, phagocytosis and clearance after phagocytosis in macrophages during early syphilis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Lin

Zhu

et al. 2020

Acad Dermatol Venereol

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Background Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum. Objective To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. Methods The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum‐treated macrophages were investigated through experiments using human monocytic cell line (THP‐1)‐derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage–treponeme mixtures. Results Activation of autophagy and phagocytosis in T. pallidum‐treated macrophages occurred in a dose‐ and time‐dependent manner. The percentage of spirochete‐positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1. Inoculation of macrophage–treponeme mixtures into rabbits showed a 3.00‐day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ2 = 5.406, P = 0.020] in the control compared with the si‐Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin‐1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group (P < 0.001)] and reduced the percentage of spirochete‐positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). Conclusion Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro. These data may be useful for understanding the host–pathogen relationship and establish the groundwork for strategies to combat syphilis.

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Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study

Abstract: We showed that robust host pro-inflammatory immune response to infection may be the predictive factor of serological cure. The treatment outcome may be also associated with the magnitude of immune reaction occurring during the treatment.

Cited by 29 publications

References 19 publications

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

Syphilis

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

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