Plasmodium falciparum infection dysregulates placental autophagy


Autoři: Flávia Afonso Lima aff001;  André Barateiro aff001;  Jamille Gregório Dombrowski aff001;  Rodrigo Medeiros de Souza aff002;  Douglas de Sousa Costa aff001;  Oscar Murillo aff001;  Sabrina Epiphanio aff003;  Lígia Antunes Gonçalves aff001;  Claudio Romero Farias Marinho aff001
Působiště autorů: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil aff001;  Multidisciplinary Centre, Federal University of Acre, Acre, Brazil aff002;  Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0226117

Souhrn

Plasmodium (P.) falciparum malaria during pregnancy has been frequently associated with severe consequences such as maternal anemia, abortion, premature birth, and reduced birth weight. Placental damage promotes disruption of the local homeostasis; though, the mechanisms underlying these events are still to be elucidated. Autophagy is a fundamental homeostatic mechanism in the natural course of pregnancy by which cells self-recycle in order to survive in stressful environments. Placentas from non-infected and P. falciparum-infected women during pregnancy were selected from a previous prospective cohort study conducted in the Brazilian Amazon (Acre, Brazil). Newborns from infected women experienced reduced birth weight (P = 0.0098) and placental immunopathology markers such as monocyte infiltrate (P < 0.0001) and IL-10 production (P = 0.0122). The placentas were evaluated for autophagy-related molecules. As a result, we observed reduced mRNA levels of ULK1 (P = 0.0255), BECN1 (P = 0.0019), and MAP1LC3B (P = 0.0086) genes in placentas from P. falciparum-infected, which was more striking in those diagnosed with placental malaria. Despite the protein levels of these genes followed the same pattern, the observed reduction was not statistically significant in placentas from P. falciparum-infected women. Nevertheless, our data suggest that chronic placental immunopathology due to P. falciparum infection leads to autophagy dysregulation, which might impair local homeostasis during malaria in pregnancy that may result in poor pregnancy outcomes.

Klíčová slova:

Autophagic cell death – Cytokines – Homeostasis – Inflammation – Malaria – Monocytes – placenta – Plasmodium


Zdroje

1. World Health Organization. World Malaria Report 2018. WHO. 2018;

2. Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):93–104. doi: 10.1016/S1473-3099(07)70021-X 17251080

3. Umbers AJ, Boeuf P, Clapham C, Stanisic DI, Baiwog F, Mueller I, et al. Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation. J Infect Dis. 2011;203(4):561–9. doi: 10.1093/infdis/jiq080 21216864

4. Bulmer JN, Rasheed FN, Francis N, Morrison L, Greenwood BM. Placental Malaria. I. Pathological Classification. Histopathology. 1993;22(3):211–8. doi: 10.1111/j.1365-2559.1993.tb00110.x 8495954

5. Rogerson SJ, Chaiyaroj SC, Ng K, Reeder JC, Brown G V. Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes. J Exp Med. 1995;182(1):15–20.

6. Fried M, Duffy PE. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996 Jun;272(5267):1502–4. doi: 10.1126/science.272.5267.1502 8633247

7. Magistrado P, Salanti A, Tuikue Ndam NG, Mwakalinga SB, Resende M, Dahlbäck M, et al. VAR2CSA Expression on the Surface of Placenta‐Derived Plasmodium falciparum-Infected Erythrocytes. J Infect Dis. 2008;198(7):1071–4. doi: 10.1086/591502 18700835

8. Abrams ET, Brown H, Chensue SW, Turner GDH, Tadesse E, Lema VM, et al. Host Response to Malaria During Pregnancy: Placental Monocyte Recruitment Is Associated with Elevated Β Chemokine Expression. J Immunol. 2003;170(5):2759–64. doi: 10.4049/jimmunol.170.5.2759 12594307

9. Rogerson SJ, Pollina E, Getachew A, Tadesse E, Lema VM, Molyneux ME. Placental monocyte infiltrates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes. Am J Trop Med Hyg. 2003;68(1):115–9.

10. Rogerson SJ, Brown HC, Pollina E, Abrams ET, Tadesse E, Lema VM, et al. Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women. Infect Immun. 2003;71(1):267–70. doi: 10.1128/IAI.71.1.267-270.2003 12496175

11. Fried M, Muga RO, Misore AO, Duffy PE. Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. J Immunol. 1998;160(5):2523–30. 9498798

12. Moormann AM, Sullivan a D, Rochford R a, Chensue SW, Bock PJ, Nyirenda T, et al. Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. J Infect Dis. 1999;180(6):1987–93. doi: 10.1086/315135 10558956

13. Ismail MR, Ordi J, Menendez C, Ventura PJ, Aponte JJ, Kahigwa E, et al. Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol. 2000;31(1):85–93. doi: 10.1016/s0046-8177(00)80203-8 10665918

14. Souza RM, Ataíde R, Dombrowski JG, Ippólito V, Aitken EH, Valle SN, et al. Placental Histopathological Changes Associated with Plasmodium vivax Infection during Pregnancy. PLoS Negl Trop Dis. 2013;7(2):e2071. doi: 10.1371/journal.pntd.0002071 23459254

15. Umbers AJ, Aitken EH, Rogerson SJ. Malaria in pregnancy: small babies, big problem. Trends Parasitol. 2011;27(4):168–75. doi: 10.1016/j.pt.2011.01.007 21377424

16. Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010 Oct;40(2):280–93. doi: 10.1016/j.molcel.2010.09.023 20965422

17. Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature. 2011;469(7330):323–35. doi: 10.1038/nature09782 21248839

18. Oh S, Roh C-R. Autophagy in the placenta. Obstet Gynecol Sci. 2017;60(3):241. doi: 10.5468/ogs.2017.60.3.241 28534010

19. Dimasuay KG, Gong L, Rosario F, McBryde E, Spelman T, Glazier J, et al. Impaired placental autophagy in placental malaria. PLoS One. 2017;12(11):1–20.

20. Saúde D de de V em S VE-S. Guia prático de tratamento da malária no Brasil. Vol. 1, Brazilian Ministry of Health. 2010. 38 p.

21. Ferreira MU, Castro MC. Challenges for malaria elimination in Brazil. Malar J. 2016;15(1):284. doi: 10.1186/s12936-016-1335-1 27206924

22. Dombrowski JG, Souza RM De, Lima FA, Bandeira CL, Murillo O, Costa D de S, et al. Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon. Jama Netw Open. 2019;2(5):e193300. doi: 10.1001/jamanetworkopen.2019.3300 31050780

23. Lucchi NW, Narayanan J, Karell MA, Xayavong M, Kariuki S, DaSilva AJ, et al. Molecular Diagnosis of Malaria by Photo-Induced Electron Transfer Fluorogenic Primers: PET-PCR. PLoS One. 2013;8(2):e56677. doi: 10.1371/journal.pone.0056677 23437209

24. Hayward CE, Lean S, Sibley CP, Jones RL, Wareing M, Greenwood SL, et al. Placental adaptation: What can we learn from Birthweight:placental weight ratio? Front Physiol. 2016;7(FEB):1–13.

25. Menendez C. Malaria during pregnancy: a priority area of malaria research and control. Parasitol Today. 1995;11(5):178–83. doi: 10.1016/0169-4758(95)80151-0 15275350

26. Chêne A, Briand V, Ibitokou S, Dechavanne S, Massougbodji A, Deloron P. Placental Cytokine and Chemokine Profiles Reflect Pregnancy Outcomes in Women Exposed to Plasmodium falciparum Infection. Infect Immun. 2014;82(9):3783–9. doi: 10.1128/IAI.01922-14 24958713

27. Kabyemela ER, Muehlenbachs A, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE. Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria. Malar J. 2008 [cited 2016 Aug 11];7:26. doi: 10.1186/1475-2875-7-26 18230163

28. Powell T, Jansson T, Dimasuay KG, Boeuf P, Beeson JG, Aitken EH, et al. Inhibition of placental mTOR signaling provides a link between placental malaria and reduced birthweight. BMC Med. 2017;15(1):1–11. doi: 10.1186/s12916-016-0759-3 28049467

29. Chandrasiri UP, Chua CLL, Umbers AJ, Chaluluka E, Glazier JD, Rogerson SJ, et al. Insight into the pathogenesis of fetal growth restriction in placental malaria: Decreased placental glucose transporter isoform 1 expression. J Infect Dis. 2014 May;209(10):1663–7. doi: 10.1093/infdis/jit803 24325968

30. Boeuf P, Aitken EH, Chandrasiri U, Chua CLL, McInerney B, McQuade L, et al. Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. PLoS Pathog. 2013 Feb;9(2):e1003153. doi: 10.1371/journal.ppat.1003153 23408887

31. Harris J. Autophagy and IL-1 family cytokines. Am J Immunol. 2013;9(1):36–42.

32. Hung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT ang. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One. 2012;7(7).

33. Oh S-Y, Choi S-J, Kim KH, Cho EY, Kim J-H, Roh C-R. Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reprod Sci. 2008 Nov;15(9):912–20. doi: 10.1177/1933719108319159 19050324

34. Curtis S, Jones CJP, Garrod A, Hulme CH, Heazell AEP. Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction. J Matern Fetal Neonatal Med. 2013 Mar;26(4):339–46. doi: 10.3109/14767058.2012.733764 23039021

35. Cao B, Macones C, Mysorekar IU. ATG16L1 governs placental infection risk and preterm birth in mice and women. JCI Insight. 2016;1(21):1–10.

36. Agrawal V, Jaiswal MK, Mallers T, Katara GK, Gilman-Sachs A, Beaman KD, et al. Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor. Sci Rep. 2015 Aug;5(1):9410.

37. Hung TH, Hsieh TT ang, Chen SF, Li MJ, Yeh YL. Autophagy in the human placenta throughout gestation. PLoS One. 2013;8(12):1–11.

38. Lucchi NW, Sarr D, Owino SO, Mwalimu SM, Peterson DS, Moore JM. Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells. Placenta. 2011 Aug;32(8):579–85. doi: 10.1016/j.placenta.2011.05.003 21632106

39. Olivier M, Van Den Ham K, Shio MT, Kassa FA, Fougeray S. Malarial Pigment Hemozoin and the Innate Inflammatory Response. Front Immunol. 2014;5(February):1–10.


Článok vyšiel v časopise

PLOS One


2019 Číslo 12