Innate Immune Response of Blood Cells in Patients With Pneumonia (ASTRAL)

Analysis of Blood Cells Innate Immune Response in Patients With Lobar Pneumonia

Pulmonary bacterial infections such as exacerbations of chronic bronchitis, nosocomial and community-acquired pneumonia represent a major public health issue. Antibiotics have shown their efficacy by direct antimicrobial activity and their limit particularly in case of multidrug-resistant microorganisms or in treating patients with aggravating pathologies. Innate immunity could be an alternative or complementary therapeutic pathway. Innate immunity receptors bind universal and invariant microbial molecular patterns present in bacteria, virus, fungus or parasite. Toll-like Receptors (TLR) activation by microbial agonist stimulates the innate immunity response which results in the production of chemokines, cytokines, antimicrobial molecules and the recruitment of innate cells.

The " Pulmonary Infection and Innate Immunity " team of the Immunity and Infection Center in Lille (Group of Dr. Sirard and Carnoy) has a long expertise in the study of TLR5 and its agonist, the flagellin, a structural protein of bacterial flagella. TLR5 is expressed on the cell surface of macrophages, monocytes, dendritic and epithelial cells. Several studies in mice have shown the flagellin prophylactic potential during bacterial infections through a TLR5 dependent stimulation of innate immunity. Recently, the group of Dr. Sirard and Carnoy has shown that flagellin can be used in association with antibiotics to treat Streptococcus pneumoniae respiratory infections in mice. The results demonstrate that an agonist of TLR can increase the therapeutic index of an antibiotic and improve the pulmonary anti-infectious reaction. This innovative approach allows us to consider new antibacterial strategies where antibiotics have reached their limit (nosocomial infection, multidrug-resistant bacteria…). TLR agonists can activate multiple human cell type. Indeed, blood cells activation by TLR agonists have been recently characterized in healthy volunteers.

However, there is no available data on the ability of TLR agonists to activate cells from patients with infectious pneumopathies. A study in these patients is inevitable if one is to consider the therapeutic use of agonists in respiratory pathologies.

Study Overview

• Status: Completed
• Conditions: Lobar Pneumonia
• Intervention / Treatment: Procedure: Blood sampling

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

• Study Contact: Name: Jean-Jacques Vitagliano, PhD; Phone Number: 03 20 22 57 51; Email: vitagliano.jean-jacques@ghicl.net

Study Locations

• France
  • Hauts De France
    • Lomme, Hauts De France, France, 59000
      • Hôpital Saint-Philibert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patient hospitalized in the department of pneumology for whom clinical, radiological and biological criteria confirm the diagnosis of lobar pneumonia

Description

Inclusion Criteria:

• Adult patient hospitalized in the department of pneumology for whom clinical, radiological and biological criteria confirm the diagnosis of lobar pneumonia
• Beneficiary of the French National Health Insurance Fund
• Signed informed consent form

Exclusion Criteria:

• Patient under guardianship
• Patient with acute respiratory distress syndrome or septic shock
• Pregnant women
• Patient with HIV, HCV or Mycobacterium tuberculosis
• Transplanted patient receiving immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
lobar pneumonia; Inpatient with lobar pneumonia will undergo a blood sampling during their hospitalization and after resolution of the infection (2 Months)	Procedure: Blood sampling; 5ml blood will be taken in addition to standard sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IL-6 specific transcripts	IL-6 specific transcripts will be measured in blood mononuclear cells after stimulation with a TLR5 agonist.	Baseline and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in expression of innate immunity genes after stimulation by TLR2 agonist		Baseline and 2 months
Change in expression of innate immunity genes after stimulation by TLR4 agonist		Baseline and 2 months
Change in expression of innate immunity genes after stimulation by TLR5 agonist		Baseline and 2 months
Change in expression of innate immunity genes after stimulation by TLR9 agonist		Baseline and 2 months
Change in ELISA assay on mediators of inflammation with stimulation by TRL2 agonist	ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL2 agonist	Baseline and 2 months
Change in ELISA assay on mediators of inflammation with stimulation by TRL4 agonist	ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL4 agonist	Baseline and 2 months
Change in ELISA assay on mediators of inflammation with stimulation by TRL5 agonist	ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL5 agonist	Baseline and 2 months
Change in ELISA assay on mediators of inflammation with stimulation by TRL9 agonist	ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL9 agonist	Baseline and 2 months
Genotyping of TLR 2 gene		Baseline
Genotyping of TLR 4 gene		Baseline
Genotyping of TLR 5 gene		Baseline
Genotyping of TLR 9 gene		Baseline

Collaborators and Investigators

• Sponsor: Lille Catholic University
• Collaborators: Institut Pasteur de Lille
• Investigators: Study Director: Christophe Carnoy, PhD, Institut Pasteur de Lille; Study Director: Jean-Claude Sirard, PhD, Institut Pasteur de Lille

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): June 24, 2020

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 26, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: RT-12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No