Host‐pathogen interaction in the tissue environment during Plasmodium blood‐stage infection

Abstract

Human malarial infection occurs after an infectious Anopheles mosquito bites. Following the initial liver‐stage infection, parasites transform into merozoites, infecting red blood cells (RBCs). Repeated RBC infection then occurs during the blood‐stage infection, while patients experience various malarial symptoms. Protective immune responses are elicited by this systemic infection, but excessive responses are sometimes harmful for hosts. As parasites infect only RBCs and their immediate precursors during this stage, direct parasite‐host interactions occur primarily in the environment surrounded by endothelial lining of blood vessels. The spleen is the major organ where the immune system encounters infected RBCs, causing immunological responses. Its tissue structure is markedly altered during malarial infection in mice and humans. Plasmodium falciparum parasites inside RBCs express proteins, such as PfEMP‐1 and RIFIN, transported to the RBC surfaces in order to evade immunological attack by sequestering themselves in the peripheral vasculature avoiding spleen or by direct immune cell inhibition through inhibitory receptors. Host cell production of regulatory cytokines IL‐10 and IL‐27 limits excessive immune responses, avoiding tissue damage. The regulation of the protective and inhibitory immune responses through host‐parasite interactions allows chronic Plasmodium infection. In this review, we discuss underlying interaction mechanisms relevant for developing effective strategies against malaria.

Dissecting Disease Tolerance in Plasmodium vivax Malaria Using the Systemic Degree of Inflammatory Perturbation

“…This dissociation argues that, except for the liver, the symptoms caused by P.vivax are strongly associated with the cytokine storm in response to infection and may be also linked to local tissue reaction, assessed by measuring levels of liver transaminases for example, but without direct interaction between these MDP levels. This dissociation can be a consequence of the immune evasion mechanisms presented by the parasite, which alter the red blood cell (RBC) structure through expression and export of molecules encoded by plasmodium genome [48]. The interaction between the changed RBC and the host immune cells hinders the plasmodium recognition and enables the tissue damage directly mediated by the pathogen.…”

“…Epidemiological aspects have largely been described to influence clinical presentation and outcomes in malaria [7,30,31,48]. Many these effects are also related to the profile of the immune response.…”

“…;[44][45][46][47][48][49][50];[39][40][41][42][43][44][45][46][47][48][49][50] years, respectively, P<0.001). No differences were noted in regard to sex distribution (P=0.43).…”

Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation

“…This dissociation argues that, except for the liver, the symptoms caused by P.vivax are strongly associated with the cytokine storm in response to infection and may be also linked to local tissue reaction, assessed by measuring levels of liver transaminases for example, but without direct interaction between these MDP values. This dissociation can be a consequence of the immune evasion mechanisms presented by the parasite, which alter the red blood cell (RBC) structure through expression and export of molecules encoded by Plasmodium genome [60]. The interaction between the modified RBC and the host immune cells may hinder the Plasmodium recognition and enables the tissue damage directly mediated by the pathogen.…”

Parasites and tissue microenvironment

“…In the liver, patrolling resident memory CD8+ T cells offer first‐line responses and current research are focused in harnessing these cells for improved vaccines. Yui et al 2 focus on the malaria erythrocytic stage and discuss how the splenic microvasculature and peripheral blood vessels offer the interface of host‐parasite interaction, and how these structures are severely altered during infection. The parasite itself contributes to modulating the host environment by expressing proteins—such as P. falciparum erythrocyte membrane protein 1 and rifins—that engage with host receptors, allowing for host evasion, or directly inhibition host responses.…”