Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections
Por:
Brito, MAM, Baro, B, Raiol, TC, Ayllon-Hermida, A, Safe, IP, Deroost, K, Figueiredo, EFG, Costa, AG, Armengol, MD, Sumoy, L, Almeida, ACG, Hounkpe, BW, De Paula, EV, Fernandez-Becerra, C, Monteiro, WM, del Portillo, HA and Lacerda, MVG
Publicada:
1 abr 2022
Resumen:
Background The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. Methods In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71(+) cell suspensions was used for sequencing and transcriptomic analysis. Results We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71(+) BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. Conclusions This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.
Filiaciones:
Brito, MAM:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
Baro, B:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain
Raiol, TC:
Fundacao Oswaldo Cruz, Fiocruz Brasilia, Brasilia, DF, Brazil
Ayllon-Hermida, A:
Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain
Safe, IP:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Deroost, K:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Francis Crick Inst, London, England
Figueiredo, EFG:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
Costa, AG:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
:
Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain
:
Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain
Almeida, ACG:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
Hounkpe, BW:
Univ Estadual Campinas, Campinas, SP, Brazil
De Paula, EV:
Univ Estadual Campinas, Campinas, SP, Brazil
Hematol & Hemotherapy Fdn Amazonas State, Manaus, Amazonas, Brazil
:
Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain
Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain
Monteiro, WM:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
:
Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain
Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain
Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
Lacerda, MVG:
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil
Univ Estado Amazonas, Manaus, Amazonas, Brazil
Fiocruz MS, Inst Leonidas & Maria Deane, Manaus, Amazonas, Brazil
Green Published, hybrid
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