BALB/c小鼠妊娠早期、中期和晚期实验性诱导疟疾过程中NK-65寄生虫血症和CD3CD4CD25Fox-p3调节性T细胞的动态变化。

Dynamics of NK-65 parasitaemia and CD3CD4CD25Fox-p3 T-regulatory cells in experimentally induced malaria during early, mid, and late-pregnancy in BALB/c mice.

作者信息

Manhas Prem Lata, Sharma Megha, Mewara Abhishek, Sachdeva Man Updesh, Sehgal Rakesh, Malhotra Pankaj

机构信息

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India.

出版信息

Indian J Microbiol. 2023 Sep;63(3):380-385. doi: 10.1007/s12088-023-01089-2. Epub 2023 Aug 26.

DOI:10.1007/s12088-023-01089-2

PMID:37781008

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10533755/

Abstract

INTRODUCTION

Malaria in pregnancy causes a dual brunt on the mother as well as the foetus. Upregulation of T-regulatory cells (Tregs) during pregnancy allows tolerance towards the growing foetus, their suppression predisposes the mother to infections. This study analyzed the levels of CD3CD4CD25Fox-p3 Tregs, parasitaemia, maternal and foetal outcomes in BALB/c mice infected with NK65 during early-, mid-, and late-pregnancy.

METHODOLOGY

Total of 114 mice, non-pregnant non-infected (n = 6), non-pregnant infected (n = 12), pregnant non-infected (n = 48) and pregnant infected (n = 48) were included in the study. Infected groups were inoculated intra-peritoneally with 1 × 10 infected RBCs during early-, mid-, and late- pregnancy (D6, D10, and D14 respectively). Six mice from each stage were sacrificed on the 5th and 7th day post-infection (DPI) to evaluate parasitaemia (staining) and Tregs from splenocytes (by flow cytometry).

RESULTS

The parasitaemia was significantly higher among early pregnancy infected mice (≥ 70%) than mid-pregnancy infected (40-70%), late pregnancy infected (50-65%), and non-pregnant infected mice (≤ 50%) ( < 0.05). The level of Tregs was significantly higher among non-pregnant infected mice as compared to non-pregnant non-infected mice (%Tregs 0.86 vs. 0.44). Among pregnant mice, the levels of Tregs in infected mice were lower than in non-infected mice during all stages of pregnancy. None of the mice infected during early- and mid-pregnancy survived at 6DPI and 7DPI, respectively, and those infected during late-pregnancy delivered premature pups.

CONCLUSION

In contrast to non-pregnant mice, the levels of Tregs among pregnant mice decrease when malaria infection is acquired thereby leading to adverse pregnancy outcomes.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12088-023-01089-2.

摘要

引言

妊娠期疟疾对母亲和胎儿都会造成双重影响。孕期调节性T细胞（Tregs）上调可使机体对发育中的胎儿产生耐受性，而对其抑制会使母亲易受感染。本研究分析了妊娠早、中、晚期感染NK65的BALB/c小鼠中CD3CD4CD25Fox-p3 Tregs水平、疟原虫血症、母体和胎儿结局。

方法

本研究共纳入114只小鼠，包括未孕未感染（n = 6）、未孕感染（n = 12）、孕未感染（n = 48）和孕感染（n = 48）小鼠。感染组在妊娠早、中、晚期（分别为第6天、第10天和第14天）经腹腔接种1×10个感染的红细胞。在感染后第5天和第7天处死每个阶段的6只小鼠，以评估疟原虫血症（染色）和脾细胞中的Tregs（通过流式细胞术）。

结果

妊娠早期感染小鼠的疟原虫血症（≥70%）显著高于妊娠中期感染（40 - 70%）、妊娠晚期感染（50 - 65%）和未孕感染小鼠（≤50%）（P < 0.05）。与未孕未感染小鼠相比，未孕感染小鼠的Tregs水平显著更高（Tregs百分比0.86对0.44）。在妊娠小鼠中，感染小鼠在妊娠各阶段的Tregs水平均低于未感染小鼠。妊娠早期和中期感染的小鼠在感染后第6天和第7天分别无一存活，妊娠晚期感染的小鼠产下早产幼崽。