ATP Induces IL-1<i>β</i>Secretion in<i>Neisseria gonorrhoeae</i>-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis

Garcia, Killen Ko; Escobar, Gisselle; Mendoza, Pablo; Beltrán, Caroll J.; Pérez, Claudio; Arancibia, Sergio; Vernal, Rolando; Rodas, Paula I.; Claudio, Acuña-Castillo; Escobar, Alejandro

doi:10.1155/2016/1258504

Cited by 7 publications

(11 citation statements)

References 60 publications

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“…Previous study indicated that NG (P9-17 strain) induced IL-1β mRNA expression in human blood monocyte-derived macrophage; however, P9-17 strain did not induce IL-1β secretion. Notably, exogenous ATP treatment induced IL-1β secretion from P9-17 strain-infected cells (31). In addition, ATP-mediated IL-1β secretion did not through increasing the caspase-1 activation in P9-17 strain-infected cells, but may act through the vesicle trafficking or pore formation levels (31).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, exogenous ATP treatment induced IL-1β secretion from P9-17 strain-infected cells (31). In addition, ATP-mediated IL-1β secretion did not through increasing the caspase-1 activation in P9-17 strain-infected cells, but may act through the vesicle trafficking or pore formation levels (31). These results were conflicting with our and other findings, as NG strains: ATCC 49226 (this study), 1291 (32) and FA1090 (14) induced IL-1β secretion without additional ATP treatment.…”

Section: Discussionmentioning

confidence: 99%

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Mechanistic Insight Into the Activation of the NLRP3 Inflammasome by Neisseria gonorrhoeae in Macrophages

Lin

Chiu

et al. 2019

Front. Immunol.

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Gonorrhea is a type III legal communicable disease caused by Neisseria gonorrhoeae (NG), one of the most common sexually transmitted bacteria worldwide. NG infection can cause urethritis or systemic inflammation and may lead to infertility or other complications. The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a protein complex composed of NLRP3, apoptosis-associated speck-like protein and caspase-1 and is an important part of the cellular machinery controlling the release of interleukin (IL)-1β and IL-18 and the pathogenesis of numerous infectious diseases. It has been reported that NG infection activates the NLRP3 inflammasome; however, the underlying mechanism remain unclear. In this report, the signaling pathways involved in the regulation of NG-mediated NLRP3 inflammasome activation in macrophages were studied. The results indicated that viable NG, but not heat-killed or freeze/thaw-killed NG, activated the NLRP3 inflammasome in macrophages through toll-like receptor 2, but not toll-like receptor 4. NG infection provided the priming signal to the NLRP3 inflammasome that induced the expression of NLRP3 and IL-1β precursor through the nuclear factor kappa B and mitogen-activated protein kinase pathways. In addition, NG infection provided the activation signal to the NLRP3 inflammasome that activated caspase-1 through P 2 X 7 receptor-dependent potassium efflux, lysosomal acidification, mitochondrial dysfunction, and reactive oxygen species production pathways. Furthermore, we demonstrated that NLRP3 knockout increased phagocytosis of bacteria by macrophages and increases the bactericidal activity of macrophages against NG. These findings provide potential molecular targets for the development of anti-inflammatory drugs that could ameliorate NG-mediated inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanistic Insight Into the Activation of the NLRP3 Inflammasome by Neisseria gonorrhoeae in Macrophages

Lin

Chiu

et al. 2019

Front. Immunol.

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“…In this line, we think that the M2 phenotype promoted by gonococcus could be reverted using COX-2 inhibitor. We also showed no significant differences in IL-1β levels in MDM infected cells compared to non-infected MDM cells, suggesting that N. gonorrhoeae could trigger insufficient IL-1β levels to activate innate immune response (83). Then, we were able to promote the IL-1β processing and release using exogenous ATP.…”

Section: Opportunities and Challenges Of Therapeutics To Control Immumentioning

confidence: 75%

“…During infection, N. gonorrhoeae interact with immune cells such as macrophages. In macrophages N. gonorrhoeae is able to escape from phagosome (27, 42, 45–48), modulate cellular iron metabolism (52, 53), inhibit apoptosis and autophagy (27, 60), modulate production of inflammatory/anti-inflammatory cytokines (63–71, 83), and polarizes macrophages, resulting in macrophages that are less capable of T cell proliferation (45). CD86, Cluster of Differentiation 86; IL- 1, Interleukin 1; IL-10, Interleukin 10; MHC, Major Histocompatibility Complex; PD-L1, Programmed Death-Ligand 1; TGF-β, Transforming Growth Factor-beta; TNF-α, Tumor Necrosis Factor-alpha.…”

Section: Resultsmentioning

confidence: 99%

Macrophage–Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation

2018

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Neisseria gonorrhoeae is a significant health problem worldwide due to multi-drug resistance issues and absence of an effective vaccine. Patients infected with N. gonorrhoeae have not shown a better immune response in successive infections. This might be explained by the fact that N. gonorrhoeae possesses several mechanisms to evade the innate and adaptative immune responses at different levels. Macrophages are a key cellular component in the innate immune response against microorganisms. The current information suggests that gonococcus can hijack the host response by mechanisms that involve the control of macrophages activity. In this mini review, we intend to condense the recent knowledge on the macrophage–N. gonorrhoeae interactions with a focus on strategies developed by gonococcus to evade or to exploit immune response to establish a successful infection. Finally, we discuss the opportunities and challenges of therapeutics for controlling immune manipulation by N. gonorrhoeae.

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“…In innate immunity, P4 downregulates IFN-γ secretion in human peripheral blood natural killer cells ( Robinson and Klein, 2012 ) and weaken macrophage functions ( Franchi et al, 2012 ). In adaptive immunity, P4 suppresses the CD4 + T cells proliferation, inhibits the cytotoxic activity of CD3 + CD8 + T cells ( García et al, 2016 ), and interferes with the polarization of Th1/Th17 cells ( Andrabi et al, 2017 ). Therefore, the immune suppression ability of P4 suggests that it may participate in the pathogenesis of female asymptomatic gonococcal infections.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models

Zhang

Gan

et al. 2021

Front. Microbiol.

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Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women.

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ATP Induces IL-1βSecretion inNeisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis

Cited by 7 publications

References 60 publications

Mechanistic Insight Into the Activation of the NLRP3 Inflammasome by Neisseria gonorrhoeae in Macrophages

Mechanistic Insight Into the Activation of the NLRP3 Inflammasome by Neisseria gonorrhoeae in Macrophages

Macrophage–Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation

Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models

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