Innate immunity to malaria—The role of monocytes

Abstract

VI.Monocytes are innate immune cells essential for host protection against malaria. Upon activation, monocytes function to help reduce parasite burden through phagocytosis, cytokine production, and antigen presentation. However, monocytes have also been implicated in the pathogenesis of severe disease through production of damaging inflammatory cytokines resulting in systemic inflammation and vascular dysfunction. Understanding the molecular pathways influencing the balance between protection and pathology is critical. In this review, we discuss recent data regarding the role of monocytes in human malaria, including studies of innate sensing of the parasite, immunometabolism, and innate immune training. Knowledge gained from these studies may guide rational development of novel antimalarial therapies and inform vaccine development.

Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype

“…Here we sought to understand the impact of P . falciparum exposure on the phenotype and function of innate immune cells, namely, the monocyte/macrophage lineage—an important source of fever-inducing pro-inflammatory cytokines during blood-stage malaria infection [ 11 ].…”

“…falciparum exposure on cells of the innate immune system, such as monocytes and macrophages, and how this may relate to the acquisition of clinical immunity. During Plasmodium blood-stage infection, circulating blood monocytes and tissue macrophages perform crucial effector functions that contribute to host defense against malaria including cytokine production, phagocytosis of infected erythrocytes, and antigen presentation [ 11 ]. However, excessive production of pro-inflammatory cytokines such IL-1β, IL-6 and TNF by monocytes/macrophages can result in systemic inflammation that causes fever and other disease manifestations of malaria [ 11 , 12 ].…”

Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes

“…Acute malaria infection is also associated with activation of monocytes through TLR-dependent responses (McCall et al, 2007;Ataide et al, 2014). Interestingly, it was demonstrated recently that in vitro exposure to Plasmodium falciparum or the parasite pigment haemozoin increased monocyte cytokine responses to re-stimulation with a TLR2 agonist (Schrum et al, 2018), leading many to theorize that malaria can induce trained immunity in humans (Ortega-Pajares and Rogerson, 2018;Dobbs et al, 2020). However, whether physiological concentrations of P. falciparum induce trained immunity in vivo has not been demonstrated.…”

Plasmodium falciparummalaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype

“…The relatively slow development of clinical immunity to malaria is associated with the gradual acquisition of P. falciparum -specific adaptive immune responses [26]. Here we sought to understand the impact of P. falciparum exposure on the phenotype and function of innate immune cells, namely, the monocyte/macrophage lineage—an important source of fever-inducing pro-inflammatory cytokines during blood-stage malaria infection [11].…”

“…Less is known about the impact of cumulative P. falciparum exposure on cells of the innate immune system, such as monocytes and macrophages, and how this may relate to the acquisition of clinical immunity. During Plasmodium blood-stage infection, circulating blood monocytes and tissue macrophages perform crucial effector functions that contribute to host defense against malaria including cytokine production, phagocytosis of infected erythrocytes, and antigen presentation [11]. However, excessive production of pro-inflammatory cytokines such IL-1β, IL-6 and TNF by monocytes/macrophages can result in systemic inflammation that causes fever and other disease manifestations of malaria [11, 12].…”