Acquired immune regulatory cells in malaria: A double-edged sword

Introduction: Malaria is one of the major public health concerns in tropical and subtropical regions of theworld. Pro-inflammatory cytokines during Plasmodium infection leads to protection and clearance of theparasite. However, excessive inflammatory responses lead to host tissue damage. Therefore, it seems necessaryto understand the mechanisms used by the immune system to create a balance between inflammatory andregulatory responses in the host. In addition, despite decades of research, there is still no effective vaccine toprevent the disease in malaria endemic areas. Therefore, our goal in this study is to review the effects of acquiredimmune regulatory cells (Breg and Treg cells) on the response and regulation of the immune system in malariainfection.Methods: In this investigation, relevant articles were reviewed by searching for the keywords "Malaria,""Breg," and "Treg" in the PubMed database and Google Scholar.Results: The results of the studies show the protective role of Breg cells by inhibiting parasite growth, inhibitinginflammation by IL-۱۰, as well as reducing the accumulation of TCD۸+ cells and NK cells in the brain andpreventing cerebral hemorrhage in mouse models. However, some studies have considered these cells to beresponsible for the growth of malaria parasites due to their suppressive roles. Such a functional duality also seenin Treg cells; On the one hand, these cells inhibit the growth of the parasite and minimize the damage to thehost tissue caused by inflammation, and on the other hand, their induction or activation during the initial phaseof infection may inhibit the inflammatory responses needed to clear the infected RBCs from the bloodcirculation and cause parasitemia, as well as reducing the cell memory response and also cause poor responseto vaccination with Plasmodium antigen.Conclusion: It appears that these cells can influence susceptibility or resistance to disease in a dynamic mannerthat is affected by the different phenotypes of these cells, differences in the species of mice and the species,strain, and pathogenicity of Plasmodium parasites used for the study, as well as the phase of disease. Therefore,it is necessary to control the factors affecting the protective function of these cells in order to design suitablevaccines to induce the clearance of malaria parasites.