Study of the innate immune response in the acute phase of human leptospirosis
This project aims to evaluate the innate immune response during the acute phase of hospital cases of human leptospirosis by assessing the proportion of activated monocyte cells (CD14+CD16+ phenotype, CD=cluster of differentiation) within the monocytes, using flow cytometry.
The research hypothesis is based on a suspected strong involvement of the immune system in the genesis of severe manifestations of the disease (hepatitis, renal failure, thrombocytopenia, intra-alveolar hemorrhage). The question raised is the state of the immune system (quantitative and qualitative: activation markers, cytokine production) assessed by studying circulating innate immune cells (monocytes, neutrophils, NK cells, dendritic cells, lymphocytes, platelets).
Background: Leptospirosis is an anthropozoonotic infectious disease responsible for various clinical presentations ranging from pauci-symptomatic forms to potentially fatal multivisceral failures. It is one of the endemic infectious pathologies of Reunion Island and is the subject of research efforts at the University Hospital of Reunion. It is also an important theme of the UMR PIMIT, which collaborates with the University Hospital.
The pathophysiology of the disease is poorly understood, with a likely involvement of the immune system in the genesis of manifestations, either for an exaggerated deleterious immune response or a deficient response, constituting a predisposition to severe forms. Thus, the immune response established during the first few days requires further evaluation. The study procedure consists of a concomitant analysis of the cellular actors of the immune system (quantitative and qualitative analysis: activation markers) and soluble factors (cytokines, chemokines, alarmins) in the acute phase of the disease. This type of approach has rarely been undertaken, as many studies focus on either cellular or soluble factors.
This overall innate immune response cannot be evaluated simply by a single criterion given the complexity of the immune response. However, a primary outcome measure is chosen as it is considered representative of the response of monocytes, major cellular actors in the early response to infection.
Secondary objectives:
- Evaluate the variation in the absolute value of CD14+CD16+ monocytes
- Assess the proportion of other activation markers on monocytes: TLR2, TLR4, CD69
- Evaluate the concentrations and proportions of circulating immune cells in the blood (neutrophils, monocytes, NK cells, dendritic cells, lymphocytes, platelets)
- Assess the levels of inflammation proteins such as cytokines, chemokines, alarmins
- Compare clinical outcome criteria of the patient based on the innate immune response (death, length of hospital stay, organ damage)
