Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection

El‐Din, Eman M. Rabie Shehab; Elgaml, Abdelaziz; Ali, Youssif M; Hassan, Ramadan

doi:10.1128/iai.00660-20

Cited by 2 publications

(2 citation statements)

References 44 publications

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“…It is well documented that E. faecalis is responsible for a serious healthcare problem and most patients infected with this pathogen suffer from severe inflammation and tissue injury. 25,26 Saccharomyces was found to be the most abundant fungal genus in human stool, followed by Malassezia and Candida. 27 Diarrhea may be associated with reduction in normal flora or a toxic effect of S. cerevisiae on the intestinal wall.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Zhou¹,

Shi²,

Fu³

et al. 2021

JIR

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Background Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear. Methods We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation. Results Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus , were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis . Conclusion Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Zhou¹,

Shi²,

Fu³

et al. 2021

JIR

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“…[46][47][48][49] Patients with an important loss of microbiota diversity have a higher risk of NRM due to a high incidence of GI GVHD. 47 Interestingly, bacteria-like Enterococcus can lead to the activation of classical complement pathway, 50 whereas other species, such as Enterobacteria, produce LPS and favors the complement lectin pathway activation. Therefore, it would be of interest to analyze gut microbiota diversity and dysbiosis in transplanted patients and correlate the results to complement activation.…”

Section: Endothelial Complications Infections and Complement Activationmentioning

confidence: 99%

Systemic complement activation influences outcomes after allogeneic hematopoietic cell transplantation: A prospective French multicenter trial

et al. 2023

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Complement activation has shown a role in murine models of graft‐versus‐host disease (GVHD) and in endothelial complications after allogeneic hematopoietic cell transplantation (allo‐HSCT). However, its impact on post‐transplant outcomes has not been so far fully elucidated. Here, we conducted a prospective multicentric trial (NCT01520623) performing serial measurements of complement proteins, regulators, and CH50 activity for 12 weeks after allo‐HSCT in 85 patients receiving a myeloablative conditioning (MAC) regimen for various hematological malignancies. Twenty‐six out of 85 patients showed an “activated” complement profile through the classical/lectin pathway, defined as a post‐transplant decline of C3/C4 and CH50 activity. Time‐dependent Cox regression models demonstrated that complement activation within the first weeks after allo‐HSCT was associated with increased non‐relapse mortality (hazard ratio [HR]: 3.69, 95% confident interval [CI]: 1.55–8.78, p = .003) and poorer overall survival (HR: 2.72, 95% CI: 1.37–5.39, p = .004) due to increased incidence of grade II–IV acute GVHD and in particular gastrointestinal (GI) GVHD (HR: 36.8, 95% CI: 12.4–109.1, p < .001), higher incidences of thrombotic microangiopathy (HR: 8.58, 95% CI: 2.16–34.08, p = .0022), capillary leak syndrome (HR: 7.36, 95% CI: 2.51–21.66, p = .00028), post‐engraftment bacterial infections (HR: 2.37, 95% CI: 1.22–4.63, p = .0108), and EBV reactivation (HR: 3.33, 95% CI: 1.31–8.45, p = .0112). Through specific immune staining, we showed the correlation of deposition of C1q, C3d, C4d, and of C5b9 components on endothelial cells in GI GVHD lesions with the histological grade of GVHD. Altogether these findings define the epidemiology and the clinical impact of complement classical/lectin pathway activation after MAC regimens and provide a rational for the use of complement inhibitory therapeutics in a post‐allo‐HSCT setting.

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Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection

Cited by 2 publications

References 44 publications

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Systemic complement activation influences outcomes after allogeneic hematopoietic cell transplantation: A prospective French multicenter trial

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