The immunology of Plasmodium vivax malaria

Abstract

Plasmodium vivax infection, the predominant cause of malaria in Asia and Latin America, affects ~14 million individuals annually, with considerable adverse effects on wellbeing and socioeconomic development. A clinical hallmark of Plasmodium infection, the paroxysm, is driven by pyrogenic cytokines produced during the immune response. Here, we review studies on the role of specific immune cell types, cognate innate immune receptors, and inflammatory cytokines on parasite control and disease symptoms. This review also summarizes studies on recurrent infections in individuals living in endemic regions as well as asymptomatic infections, a serious barrier to eliminating this disease. We propose potential mechanisms behind these repeated and subclinical infections, such as poor induction of immunological memory cells and inefficient T effector cells. We address the role of antibody‐mediated resistance to P. vivax infection and discuss current progress in vaccine development. Finally, we review immunoregulatory mechanisms, such as inhibitory receptors, T regulatory cells, and the anti‐inflammatory cytokine, IL‐10, that antagonizes both innate and acquired immune responses, interfering with the development of protective immunity and parasite clearance. These studies provide new insights for the clinical management of symptomatic as well as asymptomatic individuals and the development of an efficacious vaccine for vivax malaria.

Rosettes integrity protects Plasmodium vivax of being phagocytized

“…A cytokine storm is frequently observed in vivax malaria which is a result of an excessive activation of innate immune cells 26 . Elevated levels of pro-inflammatory cytokines have been reported in acute P. vivax infection 27,28 .…”

A distinct fingerprint of inflammatory mediators and miRNAs inPlasmodium vivaxsevere thrombocytopenia

“…Combined with the abovementioned regulatory mediators, the panels capable of differentiating PvST from other subgroups included well-known inflammatory mediators (Supplementary Table 3). A range of different cell types produces these cytokines/chemokines, which account for the cascade of events that lead to leukocytes recruitment, trafficking, and amplification of inflammation and Pv pathogenesis [8,10,40]. Interestingly, the up-regulation of IL-6 and IL-8 was critical to discriminate subgroups of vivax patients, but not from healthy subjects.…”

“…It is currently a consensus that the virulence of Pv has been underestimated [4][5][6], particularly in the presence of co-morbidities [7]. While there are critical gaps in the current knowledge of Pv pathophysiology, it is well-established that vivax malaria is associated with a systemic inflammatory response [8], perhaps more intense than its counterpart P. falciparum [7,9], which is more commonly associated with severe malaria. Findings suggest that tissue accumulation of Pv may occur, with the hidden biomass greatest in severe disease and capable of mediating systemic inflammatory response [10] [11].…”

The Interface Between Inflammatory Mediators and MicroRNAs in Plasmodium vivax Severe Thrombocytopenia

“…It is currently a consensus that the virulence of P. vivax has been underestimated (Tjitra et al, 2008;Lacerda et al, 2012;Douglas et al, 2014), particularly in the presence of co-morbidities (Anstey et al, 2012). While critical gaps in the current knowledge of P. vivax pathophysiology exist, it is well-established that vivax malaria is associated with a robust systemic inflammatory response (Antonelli et al, 2020), occasionally more intense than in infections with its counterpart P. falciparum (Yeo et al, 2010;Anstey et al, 2012), in which severe malaria typically occurs. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden biomass greatest in severe disease and capable of mediating systemic inflammation (Barber et al, 2015;Silva-Filho et al, 2020).…”