Immune exhaustion and immune anergy are underlying reasons of severe health complications in HIV-infected subjects. Treatment with anti-retroviral therapy does not fully restore the immune competence despite efficient viral suppression, and it is well known that HIV+ people are at increased risk for cancer, despite having a completely suppressed virus. We speculate that HIVinfection leads to defects in immune-resolution pathways that in turn lead to impairment of effector anti-viral responses. These immune-resolution pathways are novel pathways, so far completely unexplored in the context of HIV infection. The key cellular players in these resolution pathways are neutrophils, also the key responders to infections. Effect of neutrophil activation on effector anti-viral response has been poorly studied so far, especially in the context of HIV infection. Therefore, here we aim to undertake a study to comprehensively understand immuneprotective
and immune-pathological role of neutrophils in HIV infection. Having a unique
opportunity to study peripheral (blood) and lymphoid (lymph node) immune system will allow us to determine the effect of HIV infection on neutrophil activity and how this is linked to anti-viral effector T cell and NK cell responses at the sites of robust HIV replication (lymph node) and in systemic circulation (blood). The knowledge gained from these studies will allow us to identify new
targets for immunotherapies and could be translated to other infections.