Innate Immune Response of Blood Cells in Patients With Pneumonia

Study Overview
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Brief Summary
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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.

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

Conditions
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Lobar Pneumonia

Intervention / Treatment
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* Procedure: Blood sampling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| lobar pneumonia<br>Inpatient with lobar pneumonia will undergo a blood sampling during their hospitalization and after resolution of the infection (2 Months) | Procedure: Blood sampling<br>* 5ml blood will be taken in addition to standard sampling<br>|

What is the study measuring?
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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 |