Age-Related CD4⁺CD25⁺Foxp3⁺Regulatory T-Cell Responses During Plasmodium berghei ANKA Infection in Mice Susceptible or Resistant to Cerebral Malaria

Abstract

Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-α, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

The role of regulatory T cells during Plasmodium chabaudi chabaudi AS infection in BALB/c mice

“…Total RNA was isolated from purified Tregs (CD4 + CD25 + ), Teffs (CD4 + CD25 ‐ ) and liver tissue using TRIzol and an RNAeasy kit (Qiagen). The RNA was converted to cDNA and analysed by qPCR as previously described . mRNA expression levels were normalized to β ‐actin and relative to the mean of uninfected control samples using the cycle threshold (CT) method.…”

Phenylhydrazine administration accelerates the development of experimental cerebral malaria

“…These pro-inflammatory cytokines could together inhibit parasite growth, but may also amplify local and systemic inflammatory cascades, which, when overstimulated and uncontrolled, correlate with CM. Although Tregs, which have a suppressor role in the Th1 immune response Haque et al, 2010;Shan et al, 2013), were also significantly elevated at day 5 p.i. in PHZ-treated and PbA-infected mice, levels were not sufficient enough to control the pro-inflammatory response after the development of CM.…”

“…RNA was converted to cDNA and analyzed by qPCR as previously described (Shan et al, 2013). Levels of mRNA were normalized to a housekeeping gene, β-actin, and expressed relative to the mean of uninfected control samples using the cycle threshold (CT) method.…”

The Role of Regulatory CD4+ CD25+ T Cell Subset in Host Homeostasis during Protozoan Infection: An Overview

“…As with other protozoan parasites, host protection is rather ineffective, as Plasmodium parasites develop evasive mechanisms to hide from the immune system or subvert its mechanisms of action (reviewed by Coban et al [59]), limiting adaptive immunity and memory acquisition. Furthermore, difficulties in understanding the disease are also related to external and extrinsic factors of the host itself which influence the level of pathogenesis, such as nutritional status [60], intestinal flora [57], age [55,61,62] and ethnicity.…”