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Dynamics of Plasmodium berghei NK-65 parasitaemia and CD3+CD4+CD25+Fox-p3+ T-regulatory cells in experimentally induced malaria during early, mid, and late-pregnancy in BALB/c mice

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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 CD3+CD4+CD25+Fox-p3+ Tregs, parasitaemia, maternal and foetal outcomes in BALB/c mice infected with P. berghei 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 × 106 P. berghei 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%) (p < 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.

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Fig. 1

Data availability

None.

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Acknowledgements

We would like to thank ICMR for funding this work. We wish to thank Dr. Monika, Mr. Jaspal, Mr.Ravi, Mr. Rajan, and Ms. Tripti for the help they provided during animal housework. We are thankful to Mrs. Parveen Boss and Mrs. Meenakshi for helping in flow cytometry experiments. We would also like to thank Hardeep, Dr. Vimal, and Dr.Tanveer for helping in editing the paper.

Funding

This work was supported by ICMR and PGIMER, Chandigarh. Prem Lata was a Ph.D. student at the Post Graduate Institute of Medical Education and Research and had an ICMR-JRF fellowship.

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Authors and Affiliations

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

    Prem Lata Manhas & Pankaj Malhotra

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

    Megha Sharma, Abhishek Mewara & Rakesh Sehgal

  3. Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Bilaspur, Himachal Pradesh, India

    Megha Sharma

  4. Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Man Updesh Sachdeva

  5. Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Pankaj Malhotra

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  1. Prem Lata Manhas
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Contributions

Study concept: PM, RS; Data collection: PLM, MUS; Data analysis and curation: PLM, MS, AM, MUS; Writing of manuscript: PLM, MS; Revision of manuscript: MS, PLM, AM, PM; Study supervision: PM, RS.

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Correspondence to Rakesh Sehgal or Pankaj Malhotra.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Megha Sharma was affiliated to second at the start and to third by the end of the study.

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Manhas, P.L., Sharma, M., Mewara, A. et al. Dynamics of Plasmodium berghei NK-65 parasitaemia and CD3+CD4+CD25+Fox-p3+ T-regulatory cells in experimentally induced malaria during early, mid, and late-pregnancy in BALB/c mice. Indian J Microbiol 63, 380–385 (2023). https://doi.org/10.1007/s12088-023-01089-2

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