3033 – DIFFERENTIAL RESPONSES AND RECOVERY DYNAMICS OF HAEMATOPOIETIC POPULATIONS FOLLOWING PLASMODIUM CHABAUDI INFECTION

Mature immune cells are continuously replenished through haematopoiesis. At the top of the hematopoietic system, a pool of haematopoietic stem cells (HSCs) sustains this process by giving rise to several different progenitors thanks to their self-renewal and multipotent capacities. HSCs and downstream progenitors (HSPCs) reside within the bone marrow in a tightly regulated environment where proliferation and quiescence are finely balanced. Upon haematopoietic stress, such as severe infection, HSCs exit quiescence to respond to the increased demand of immune cells, leading to disrupted haematopoiesis. This disruption has been mainly studied during the acute phase of stress, however the process and level of HSPCs recovery is not fully understood yet. Here we employ a self-recovery rodent model of malaria, Plasmodium chabaudi, to systematically assess disease-induced changes in the different haematopoietic populations as well as investigating their recovery. Via phenotypic, proliferation and functional analysis we demonstrated that quiescent l HSCs are activated and depleted during the acute phase of infection, while the multipotent progenitor compartments are drastically enlarged. Despite all the compartments presenting an enhanced proliferation, homeostasis levels were reached upon pathogen clearance. Interestingly, we found that more mature progenitor populations (CMP, GMP, MEP, CLP) virtually disappear at the peak of the infection and make a slower return to control levels compared to more primitive HSPCs. The percentages of proliferating cells within these more committed progenitors were consistently similar to control levels throughout the infection. Our data demonstrate that HSPCs adopt different responses to cope with severe infection and suggest that the ability to adjust proliferative capacity becomes more restricted alongside the lineage commitment process.