NLRP3 inflammasome is involved in the recognition of Paracoccidioides brasiliensis by human dendritic cells and in the induction of Th17 cells

Castro, Lívia Furquim de; Longhi, L; Paião, Munir Regini; Justo-Júnior, Amauri da Silva; Jesus, Marcelo Bispo de; Blotta, Maria Heloı́sa Souza Lima; Mamoni, Ronei Luciano

doi:10.1016/j.jinf.2018.03.004

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…Although they both increase significantly following SCI, CRID3 has no significant effect on their numbers and proportions. This is consistent with the recent reports, which demonstrated that inflammasome activation can destroy Th1/Th2 balance, produce predominant Th1/Th17 inflammatory response, and inhibiting inflammasome activation can restore the Th1/Th2 balance [70][71][72].…”

Section: Discussionsupporting

confidence: 93%

CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment

Chen

Wang

Shi

et al. 2020

J Neuroinflammation

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Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis-associated speck-like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. Here, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI. Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation, and functional recovery were assessed. Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β, and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior have also been found. Conclusions: CRID3 may ameliorate murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance, and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI.

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Section: Discussionsupporting

confidence: 93%

CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment

Chen

Wang

Shi

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

CRID3, a Blocker of Apoptosis Associated Speck Like Protein Containing a Card, Ameliorates Murine Spinal Cord Injury by Improving Local Immune Microenvironment

et al. 2020

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demonstrated that inflammasomes may play an important role in the inflammation of SCI. Because ASC is the adaptor protein shared by inflammasomes, we speculated that ASC can be used as a target to inhibit the activation of inflammasomes, so as to improve the local immune microenvironment of SCI and reduce nerve damage. In this study, CRID3, a blocker of ASC oligomerization [18], was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI. Methods Animals A total of 120 female C57BL/6 mice (weight, 18-20 g; age, 8 weeks old) obtained from Chang Zhou Cavens Laboratory Animal Ltd. Animals were housed in ventilated cages and maintained on a 12-hour light/dark cycle with ad libitum access to food and water. Ambient room temperature was maintained at 20 ~ 22 °C with 30 ~ 70% humidity. Animal care following surgery complied with the regulations for the management of experimental animals (revised by the Ministry of Science and Technology of China in June 2004). The study was approved by the Institutional Committee on Animal Care, Use and Research of the Bengbu Medical College. Contusive SCI and drug injection. An Infinite Horizon impactor (Precision Systems & Instrumentation) was used to perform contusive SCI, as previously described [19, 20]. The mice were first anesthetized with a cocktail of ketamine (80 mg/kg)/xylazine (10 mg/kg) intraperitoneally injection and then the T9 lamina was excised. The spine was stabilized by clamping the T7 and T11 spinous processes, and then a moderate SCI model was created using a rod (1.3 mm in diameter) with a force of 50 Kdynes. Sham-operated (sham) mice only received a laminectomy without contusive injury. Post-surgically, mice were placed in a temperature-and humidity-controlled chamber. Manual bladder emptying was performed three times daily until reflex bladder emptying was established. To prevent infections, animals were daily provided with chloramphenicol (50 mg/kg) via drinking water. The spinal cord-injured mice were randomly assigned to the vehicle control or CRID3 injection groups. Mice were intraperitoneally injected with 0.01 M PBS (pH 7.4) or CRID3 (Target Molecule Corp., 50 mg/kg prepared in PBS)

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“…Because DOTAP can activate DCs via the ROS pathway, the ROS pathway may play a role in regulating the TLR2 and TLR9 pathways. Because the ROS pathway can upregulate IL-1β production [27], we suggested that the ROS pathway may be involved in the induction of IL-1β production by the rlipoE7m plus POCpG/DOTAP combined treatment. Moreover, IL-1β can promote DC maturation and enhance the secretion of IL-12 to induce a Th1-biased immune response [28,29].…”

Section: Discussionmentioning

confidence: 91%

Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells

Shen

Liu

et al. 2020

Cancers

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Dendritic cells (DCs) are antigen-presenting cells involved in T cell activation and differentiation to regulate immune responses. Lipoimmunogens can be developed as pharmaceutical lipoproteins for cancer immunotherapy to target DCs via toll-like receptor 2 (TLR2) signaling. Previously, we constructed a lipoimmunogen, a lipidated human papillomavirus (HPV) E7 inactive mutant (rlipoE7m), to inhibit the growth of HPV16 E7-expressing tumor cells in a murine model. Moreover, this antitumor effect could be enhanced by a combinatory treatment with CpG oligodeoxynucleotides (ODN). To improve safety, we developed a rlipoE7m plus DOTAP liposome-encapsulated native phosphodiester CpG (POCpG/DOTAP) treatment to target DCs to enhance antitumor immunity. We optimized the formulation of rlipoE7m and POCpG/DOTAP liposomes to promote conventional DC and plasmacytoid DC maturation in vitro and in vivo. Combination of rlipoE7m plus POCpG/DOTAP could activate conventional DCs and plasmacytoid DCs to augment IL-12 production to promote antitumor responses by intravenous injection. In addition, the combination of rlipoE7m plus POCpG/DOTAP could elicit robust cytotoxic T lymphocytes (CTLs) by intravenous immunization. Interestingly, the combination of rlipoE7m plus POCpG/DOTAP could efficiently inhibit tumor growth via intravenous immunization. Moreover, rlipoE7m plus POCpG/DOTAP combined reduced the number of tumor-infiltrating regulatory T cells dramatically due to downregulation of IL-10 production by DCs. These results showed that the combination of rlipoE7m plus POCpG/DOTAP could target DCs via intravenous delivery to enhance antitumor immunity and reduce the number of immunosuppressive cells in the tumor microenvironment.

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NLRP3 inflammasome is involved in the recognition of Paracoccidioides brasiliensis by human dendritic cells and in the induction of Th17 cells

Cited by 25 publications

References 29 publications

CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment

CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment

CRID3, a Blocker of Apoptosis Associated Speck Like Protein Containing a Card, Ameliorates Murine Spinal Cord Injury by Improving Local Immune Microenvironment

Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells

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