P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.

A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1) cell differentiation to the detriment of follicular T helper (Tfh) cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.

Inhale, exhale: Why particulate matter exposure in animal models are so acute? Data and facts behind the history.

We present a dataset obtained by extracting information from an extensive literature search of toxicological experiments using mice and rat animal models to study the effects of exposure to airborne particulate matter (PM). Our dataset covers results reported from 75 research articles considering paper published in 2017 and seminal papers from previous years. The compiled data and normalization were processed with an equation based on a PM dosimetry model. This equation allows the comparison of different toxicological experiments using instillation and inhalation as PM exposure protocols with respect to inhalation rates, concentrations and PM exposure doses of the toxicological experiments performed by different protocols using instillation and inhalation PM as exposure methods. This data complements the discussions and interpretations presented in the research article "Inhale, exhale: why particulate matter exposure in animal models are so acute?" Curbani et al., 2019.

Inhale, exhale: Why particulate matter exposure in animal models are so acute?

Ecotoxicological studies that try to describe the effects of particulate matter (PM) on human health are important in order to gain a deeper understanding of their effects in disease outcomes. Because exposure protocols are not easily comparable, evaluating human PM exposure is a difficult task. Thus, interpreting ambiguous or conflicting results from different experiments could lead to misleading conclusions about the true nature of PM effects. To address these issues, we compiled a collection of relevant research articles in order to compare present PM exposure methods and extract data related to concentration, inhalation rates (IR), and doses. We also compare the experimental exposure levels reported in these articles to PM levels around the world. In particular, our dataset covers reported results from 75 research articles. To allow for comparison between protocols, we used this data to fit a normalization equation that depends upon concentration, exposure time, dose, inhalability, and physiological parameters. Based on the collected research papers, instillation is the prevalent exposure method. Also, the median PM IR from these experiments is three orders of magnitude higher than the PM IR found in environmental conditions (EAP). Experiments employing inhalation of concentrated PM show IR results that are two orders of magnitude higher than EAP; these results are cause for concerns, since the PM exposure were acute, sudden, and higher than the worst-case exposure scenarios reported by the world megacities. We also found that different PM exposure protocols are sources for the observed variability in physiological response results found from animal models. We discuss these findings and make suggestions for future exposure methodologies. Such considerations should be valuable for quantifying PM exposure in disease outcomes.