Complement C4, Infections, and Autoimmune Diseases

Wang, Hongbin; Liu, Mengyao

doi:10.3389/fimmu.2021.694928

Cited by 65 publications

(55 citation statements)

References 161 publications

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“…ENSOARG00000002722 encodes complement C4-like protein, which is the key molecule in the complement system. Complement C4 is one of the chief constituents of innate immunity for immediate recognition and elimination of invading microbes, and plays an essential role in the functions of both classical and lectin complement pathways ( 47 ). ARHGEF2 encodes the microtubule-associated immune molecule guanine nucleotide exchange factor-H1 (GEF-H1), which is crucial in coupling microtubule dynamics to the initiation of microtubule-mediated immune responses ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

et al. 2022

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Ovine and caprine brucellosis, both caused by Brucella melitensis, lead to substantial economic losses in the animal industry and health problems in human populations. Brucella suis strain 2 (B.suis S2), as a live attenuated vaccine, is used extensively in China to prevent brucellosis. It has been proven that microRNA (miRNAs) are involved in the immunopathogenesis of brucellosis; however, the miRNA-driven mechanism of immune response to B.suis S2 in vivo remains unknown. To determine which new miRNAs are involved in the host immune response to B.suis S2 and elucidate the function of these miRNAs, we performed a comprehensive analysis of miRNA expression profiles in sheep immunized with B.suis S2 using the high-throughput sequencing approach. The submandibular lymphatic nodes from sheep seropositive for Brucella were collected at 7, 14, 21, 30, 60 and 90 days post-immunization. MiRNA sequencing analysis revealed that 282 differentially expressed miRNAs (|log2 fold-change |>0.5 and p < 0.05) were significantly enriched in the immune pathways, including the NF-kappa B signaling pathway, B cell receptor signaling pathway, p53 signaling pathway and complement and coagulation cascades. Increasing the threshold to |log2 fold change|>1 and p < 0.01 revealed 48 differentially expressed miRNAs, 31 of which were novel miRNAs. Thirteen of these novel miRNAs, which were differentially expressed for at least two time points, were detected via RT-qPCR assays. The novel_229, novel_609, novel_973 and oar-miR-181a assessed by RT-qPCR were detectable and consistent with the expression patterns obtained by miRNA sequencing. Functional analyses of these miRNAs demonstrated that their target genes participated in the immune response pathways, including the innate and adaptive immunity pathways. The immune-related target genes of novel_229 included ENSOARG00000000649 and TMED1, as well as LCN2, PDPK1 and LPO were novel_609 target genes. The immune-related target genes of novel_973 included C6orf58, SPPL3, BPIFB1, ENSOARG00000021083, MPTX1, CCL28, FGB, IDO1, OLR1 and ENSOARG00000020393. The immune-related target genes of oar-miR-181a included ENSOARG00000002722, ARHGEF2, MFAP4 and DOK2. These results will deepen our understanding of the host miRNA-driven defense mechanism in sheep immunized with B.suis S2 vaccine, and provide the valuable information for optimizing vaccines and developing molecular diagnostic targets.

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Section: Discussionmentioning

confidence: 99%

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

et al. 2022

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“…Pleural effusion adenosine deaminase (ADA)can be used to distinguish between Gram-negative and Gram-positive infections of the pleural cavity early and quickly [19]. Complement C4 (CO4) is a key molecule in the complement system and one of the main components of innate immunity, which can immediately identify and eliminate invading microorganisms [20]. Apolipoprotein E (APOE) was a novel diagnostic marker for invasive bacterial infections in pediatric patients [21].…”

Section: Discussionmentioning

confidence: 99%

Comparison of urine proteome among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria

2021

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Purpose To explore and compare urine proteome changes among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria. Method Escherichia coli and Staphylococcus aureus are two common human pathogens. Three rat models were established: (i) the intraperitoneal co-injection of E. coli and S. aureus model (ES model), (ii) intraperitoneal injection of E. coli model (E model), and (iii) intraperitoneal injection of S. aureus model (S model). Urinary proteomes on days 0, 1 and 2 of the three models were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Results A total of 111, 34 and 94 differential proteins were identified in the ES model, E model and S model, respectively. Among them, some differential proteins were reported to be associated with bacterial infection. Approximately 47% differential proteins in the E model overlapped with ES model, and 37% differential proteins in the S model overlapped with ES model. Compared with the E model and S model, a total of 71 unique differential proteins were identified in the ES model. Conclusion Our results indicated that (1) the urine proteome could distinguish different bacterial intraperitoneal injections models and (2) the effects of co-injection with two bacteria on the urine proteome were not simple superposition of single injection.

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“…However, C1q deposition in the liver did not increase significantly after BDL (Figure 2A), suggesting that complement activation in CLI is not mediated through the classical pathway. Although C4 is necessary for the formation of C3 convertase in both the classical and lectin pathways and C4 deficiency leads to inhibition of these two pathways (27), its deficiency had no effect on C3 activation in the BDL mouse model (Figure 2B). Factor B is critical for activation of the alternative pathway (28).…”

Section: The Alternative Pathway Contributes To Over-activation Of Complement In Mice With CLImentioning

confidence: 99%

Complement Inhibition Alleviates Cholestatic Liver Injury Through Mediating Macrophage Infiltration and Function in Mice

Guo

Chen

Zeng³

et al. 2022

Front. Immunol.

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Background and AimsCholestatic liver injury (CLI), which is associated with inflammatory reactions and oxidative stress, is a serious risk factor for postoperative complications. Complement system is involved in a wide range of liver disorders, including cholestasis. The present study assessed the role of complement in CLI and the therapeutic effect of the site-targeted complement inhibitor CR2-Crry in CLI.MethodsWild-type and complement gene deficient mice underwent common bile duct ligation (BDL) to induce CLI or a sham operation, followed by treatment with CR2-Crry or GdCl3. The roles of complement in CLI and the potential therapeutic effects of CR2-Crry were investigated by biochemical analysis, flow cytometry, immunohistochemistry, ELISA, and quantitative RT-PCR.ResultsC3 deficiency and CR2-Crry significantly reduced liver injuries in mice with CLI, and also markedly decreasing the numbers of neutrophils and macrophages in the liver. C3 deficiency and CR2-Crry also significantly reduced neutrophil expression of Mac-1 and liver expression of VCAM-1. More importantly, C3 deficiency and CR2-Crry significantly inhibited M1 macrophage polarization in these mice. Intravenous injection of GdCl3 inhibited macrophage infiltration and activation in the liver. However, the liver injury increased significantly. BDL significantly increased the level of lipopolysaccharide (LPS) in portal blood, but not in peripheral blood. GdCl3 significantly increased LPS in peripheral blood, suggesting that macrophages clear portal blood LPS. Oral administration of ampicillin to in GdCl3 treated mice reduced LPS levels in portal blood and alleviated liver damage. In contrast, intraperitoneal injection LPS increased portal blood LPS and reversed the protective effect of ampicillin. Interestingly, C3 deficiency did not affect the clearance of LPS.ConclusionsComplement is involved in CLI, perhaps mediating the infiltration and activation of neutrophils and macrophage M1 polarization in the liver. C3 deficiency and CR2-Crry significantly alleviated CLI. Inhibition of complement could preserve the protective function of macrophages in clearing LPS, suggesting that complement inhibition could be useful in treating CLI.

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Complement C4, Infections, and Autoimmune Diseases

Cited by 65 publications

References 161 publications

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With the Brucella suis Strain 2 Vaccine

Comparison of urine proteome among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria

Complement Inhibition Alleviates Cholestatic Liver Injury Through Mediating Macrophage Infiltration and Function in Mice

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