Overview
Natural Killer (NK) cells play a large role in the innate immune response as they are equipped to kill infected or tumor cells. They express a panel of activating and inhibitory receptors that regulate the destruction of the target cell. Many reports have shown that NK cell function is suppressed in CHB patients. Exhaustion occurs when activating receptors become over stimulated leading to the loss of NK function. The investigators hypothesize that NK cells are rendered dysfunctional/ exhausted by HBV. The primary objective is to determined the phenotypical modifications and mechanisms associated to NK cell dysfunction, during different phases of CHB infection, in not treated patients.
Description
Using a previous cohort from the Limoges Hospital, the investigators have identified by multi-parametric flow cytometry phenotypic, cytokine and signaling molecules that are altered in NK cells from CHB patients during the inactive phase. Phenotypic changes observed include the downregulation of CD160, NKp30, CD16 and Tim-3. The expansion of 'adaptive' NK cells (FCεRg- NKG2C+ or CD57hi), and the upregulation of CD107a (steady state), NKG2D and 41BB. Functional changes include the decrease in the levels of IFNγ, TNFα and MIP1β. Cellular metabolism is now recognized to regulate functional properties of immune cells such as T or NK cells. The mammalian target of rapamycin (mTOR) kinase is a key regulator of cellular metabolism, integrating environmental cues to control downstream metabolic pathways. mTOR is the catalytic subunit of two different complexes: mTORC1 and mTORC2, the activity of which can be measured by measuring the level of phosphorylation of the proteins S6 and Akt respectively. The lab has previously shown that the mTOR pathway regulates NK cell development and activation 2. The investigators have observed that pS6 and pAkt are also decreased in CHB patients.
Eligibility
Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible for participation
in this study:
- Male or female, age ≥18 years
- HBV infection or chronic HBV infection
- Willing and able to provide written informed consent
Healthy donors must meet all of the following inclusion criteria to be eligible for
participation in this study:
- Male or female, age between 18 and 50 years
- Willing and able to provide written informed consent
Exclusion Criteria:
- Subjects who meet any of the following exclusion criteria are not to be enrolled in
this study:
- Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
- Chronic liver disease of a non-HBV etiology
- Immune or cancerous disease