Soluble IL-2Rα correlates with imbalances of Th1/Th2 and Tc1/Tc2 cells in patients with acute brucellosis

Sun, Huali; Ma, Chang–Jin; Du, Xiu‐Fang; Yang, Siyuan; Xiao, Le; Zhao, Hong; Wang, Ling-Hang; Tang, Yuling; Li, Xingwang; Jiang, Rongmeng

doi:10.1186/s40249-020-00699-y

Cited by 6 publications

(7 citation statements)

References 34 publications

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“…This means Tc1 may trigger IFN-γ primed macrophage populations to secrete pro-inflammatory cytokines such as IL-1β, which promotes aggravating intrauterine inflammation and contributes to placental dysfunction. One recent study suggested that the clearance of Brucella requires IFN-γ-mediated type-1 T cell (Th1/Tc1) immune responses ( 38 , 39 ), while the IL-4, IL-10, Th2/Tc2 response determines susceptibility to Brucella and disease severity ( 40 , 41 ). In another study, in vitro -generated tumor-reactive Tc2 cells were less efficient in eliminating lung tumors than Tc1 cells ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

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Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation

Liu

Panda

et al. 2021

Front. Immunol.

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CD8+ T cells recognize non-self antigen by MHC class I molecules and kill the target cells by the release of proinflammatory cytokines such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Our group previously reported an increase of CD8+ T‐cell trafficking in the placenta with exposure to Lipopolysaccharides (LPS). CD8+ cytotoxic T cells have been classified into distinct subsets based upon cytokine production: Tc1 cells produce IFN-γ, Tc2 cells produce interleukin 4 (IL-4). Accordingly, the purpose of this research is to analyze the subsets of placenta CD8+ T cells. We hypothesized that LPS injection would induce a change of properties of CD8+ T cell and Tc1/Tc2 ratio. We investigated the subsets of CD8+ T cell infiltration to placenta and their specific function in response to LPS-induced inflammation in a mouse model. At embryonic (E) day 17, pregnant CD-1 dams received an intrauterine injection of 25 µg LPS in100 μl PBS or 100 μl of PBS only. Flow cytometry was used to quantify CD8+ T cells, evaluate the phenotype and subtypes, and detect markers of Tc1 and Tc2 cells in placenta, at 6 hours and 24 hours post injection (hpi). Intracellular staining and flow cytometry were performed to characterize cytokines produced by CD8+ T cells. Standard statistical analysis were employed. After 6 and 24 hours of LPS injection, total CD8 T cells increased (P<0.05). Tc1 cells expanded (P<0.05) in LPS-treated dams compared with the PBS group. The Tc1/Tc2 ratio was significantly higher in the LPS group than the PBS group (P<0.05). The expression of TNF-α and IFN-γ were increased in LPS group both at 6hpi and 24 hpi (P<0.05). We identified functional placental CD8+ T cell subtypes and found a significant increase ratio of Tc1/Tc2. Following IUI, CD8+ T cells induced inflammatory response in the placenta primarily via the production of Type 1 cytokines such as IFN-γ and TNF-α. We have provided evidence of a Tc1-bias response and cytokines in the mouse model of IUI.

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Section: Discussionmentioning

confidence: 99%

“…An imbalance between the production of Tc1 and Tc2 cytokines contributes to an impairment in T cell-mediated immunity, which may ultimately impact anti-bacterial immune responses ( 41 ). In this study, we observed a loss of homeostasis between placental Tc1, Tc2, and their cytokine production following LPS intrauterine administration.…”

Section: Discussionmentioning

confidence: 99%

Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation

Liu

Panda

et al. 2021

Front. Immunol.

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“… 12 , 16 , 18 This result may support our previous study results indicating elevated percentages of Th1 and Th2 cells in patients with acute brucellosis. 17 Th17 cells are induced by IL-6, IL-21, and TGF-β, and IL-17A is the major effector molecule of Th17 cells. 24 IL-17A is a pro-inflammatory cytokine that promotes the protective immune response against bacterial infections but mediates tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] In human brucellosis, increasing evidence suggests that infection induced by Brucella disrupts cytokine expression and function of the CD4 + Th and CD8 + cytotoxic T cells and that infection progression is mainly associated with Th2 cytokines. 16,17 In particular, TNF-α, IFN-γ, IL-2, and IL-10 levels are affected during Brucella infection. 16,18,19 Additionally, the level of these cytokine indicates the status of the immune response and disease progression.…”

Section: Introductionmentioning

confidence: 99%

“…However, the role of Th1/Th2/Th17 cytokines in acute brucellosis infection and treatment still remains partially defined or debated. [16][17][18][19][20] In this prospective cohort study, we enrolled 30 patients with acute brucellosis and estimated changes in the serum levels of seven general Th1/Th2/Th17 cytokines during treatment by using cytometric bead array (CBA); healthy controls matched by age and sex were also included in the study. Furthermore, we followed up the treated individuals for 6 months.…”

Section: Introductionmentioning

confidence: 99%

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Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment

Tang¹,

Ma²,

Sun³

et al. 2021

IDR

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Purpose Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. Patients and Methods Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. Results In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). Conclusion Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.

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Research progress in the therapy of brucellosis

Wang

Peng

2023

Animal Research and One Health

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Brucellosis is a zoonotic bacterial disease posing serious threats to the health of humans and animals. Currently, effective therapeutics available for brucellosis are in urgent demand. Brucellosis is transmitted to humans through diet or contact with infected animals. Several live‐attenuated vaccine strains are commercially available for animals, such as Brucella melitensis Rev.1, Brucella abortus S19, and RB51. However, no secure and effective vaccine for human beings has been developed yet against brucellosis, for which antibiotic therapy is the most frequently used and valid. Nevertheless, excessive antibiotics could prohibit the sensitivity of Brucella and develop resistance in humans. In addition, other clinical treatments, such as surgical treatment, have little effect on brucellosis. Therefore, novel treatment protocols should be explored. Based on numerous experimental studies, it is speculated that brucellosis can be fundamentally treated by inhibiting the activation of the type IV secretion system and changing the acidic environment of eBCV. In addition, previous literature showed that traditional Chinese medicine therapy also had certain efficacy, providing a new perspective angle for the exploration of treatment options.

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Soluble IL-2Rα correlates with imbalances of Th1/Th2 and Tc1/Tc2 cells in patients with acute brucellosis

Cited by 6 publications

References 34 publications

Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation

Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation

Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment

Research progress in the therapy of brucellosis

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