Plasmodium falciparum induces apoptosis in human mononuclear cells

Abstract

The level of spontaneous apoptosis in short-term lymphocyte cultures was evaluated in different human immunodeficiency virus-negative groups of either healthy control individuals or patients with clinical malaria. The mean percentage of spontaneous apoptosis found in patients during a malaria attack was significantly higher than in sex-and age-matched healthy controls. The healthy asymptomatic controls were individuals with different degrees of exposure to Plasmodium falciparum as reflected by their various mean levels of specific anti-P. falciparum (immunoglobulin G and M) antibodies. The percentages of apoptotic nuclei were found to be significantly higher in lymphocytes from subjects living in an area where malaria is holoendemic than in lymphocytes from subjects less exposed. Concentrations of soluble plasma interleukin-2 receptor were also higher in subjects from areas where malaria is endemic than in other groups, revealing different levels of lymphocyte activation. Of particular relevance to the in vivo situation, a P. falciparum schizont-rich extract induced a systematic and significant elevation of apoptotic nuclei at day 6 in 87.5% (35 of 40) of the subjects tested. In additional studies with different concentrations of extract, [ 3 H]thymidine incorporation was concomitant with a low or limited level of apoptosis. Taken together, our results strongly suggest that acute as well as chronic asymptomatic P. falciparum infections were consistently associated with a marked increase in the level of mononuclear cell apoptosis. This process could be implicated in some of the alterations reported for the proliferative T-cell responses in areas where malaria is endemic.

Eimeria tenellaROPkinaseEtROP1induces G0/G1 cell cycle arrest and inhibits host cell apoptosis

“…This is fully consistent with our findings: EtROP1 wt overexpression induced (Cui et al, 2016). This dual activity was also described for other apicomplexan parasites such as Plasmodium, Toxoplasma, Theileria, Cryptosporidium (Goebel, Gross, & Luder, 2001;Guergnon, Dessauge, Langsley, & Garcia, 2003;Heussler et al, 1999;Leiriao et al, 2005;McCole, Eckmann, Laurent, & Kagnoff, 2000;Nash et al, 1998;ToureBalde et al, 1996) supporting a mechanism shared within the phylum (Luder, Stanway, Chaussepied, Langsley, & Heussler, 2009). The mechanism by which parasite protects cells from induction of apoptosis has been partially deciphered: in T. gondii model, the dense granule TgGRA16 alters host p53 levels, in a HAUSP-dependent manner (Bougdour et al, 2013;Chang et al, 2015).…”

Splenocyte apoptosis in Plasmodium berghei ANKA infection: possible role of TNF‐α and TGF‐β

“…The flow cytometric analyses revealed increase in splenocytes located at the sub-G0/G1 phase of the cell cycle during peak parasitaemia period; this outcome could be indicative of ongoing cell cycle arrest or, based upon annexin V staining patterns here, an increase in apoptotic events among the splenocytes was noted compared with controls. There are reports that apoptosis is increased during malarial infections in the hosts (6,17,56,57), which may also mediate the severity of malaria. It is therefore quite plausible that the increases in apoptosis among splenocytes and of greater importance, potentially T and B lymphocytes (58-60) (data not shown for future study), could be a key factor underlying the pathological change evolved after the PbA infection.…”

Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway

“…But apoptosis in liver during malarial infection has been overlooked. However, malaria-induced apoptosis in other cellular systems has been studied in mice (38), monkeys (39) and human (40). Dramatic cellular changes take place in the spleen during malarial infection and Fas mediated apoptotic T cells, B cells and macrophages are found in the spleen (38).…”

“…Dramatic cellular changes take place in the spleen during malarial infection and Fas mediated apoptotic T cells, B cells and macrophages are found in the spleen (38). In vitro studies with human peripheral blood mononuclear cells from patients with acute Plasmodium falciparum malaria have also demonstrated the incidence of apoptosis (40). Moreover Plasmodium chabaudi infection in mice induces apoptosis in spleen and thymus (41).…”