Author | Santos, Alessandro Marins dos | |
Author | Silva, Jackline de Paula Ayres | |
Author | Antunes, Dina | |
Author | Moreira, Carlos José de Carvalho | |
Author | Machado, Marcelo Pelajo | |
Author | Alfaro, David | |
Author | Zapata, Agustin G. | |
Author | Bonomo, Adriana Cesar | |
Author | Savino, Wilson | |
Author | Meis, Juliana de | |
Author | Oliveira, Désio Aurélio Farias de | |
Access date | 2022-04-18T20:11:36Z | |
Available date | 2022-04-18T20:11:36Z | |
Document date | 2022 | |
Citation | SANTOS, Alessandro Martins dos et al. Oral Trypanosoma cruzi Acute Infection in Mice Targets Primary Lymphoid Organs and Triggers Extramedullary Hematopoiesis. Frontiers in Cellular and Infection Microbiology, v. 12, Article 800395, p. 1-12, Mar. 2022. | pt_BR |
ISSN | 2235-2988 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/52335 | |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Infecção oral | pt_BR |
Subject in Portuguese | Medula óssea | pt_BR |
Subject in Portuguese | Timo | pt_BR |
Subject in Portuguese | Hematopoiese | pt_BR |
Subject in Portuguese | Células-tronco hematopoiéticas | pt_BR |
Subject in Portuguese | Hematopoiese extramedular | pt_BR |
Subject in Portuguese | Fluxo multiparamétrico | pt_BR |
Title | Oral Trypanosoma cruzi Acute Infection in Mice Targets Primary Lymphoid Organs and Triggers Extramedullary Hematopoiesis | pt_BR |
Type | Article | |
DOI | 10.3389/fcimb.2022.800395 | |
Abstract | During the acute phase of Chagas disease, Trypanosoma cruzi circulation through the bloodstream leads to high tissue parasitism in the host. In primary lymphoid organs, progenitor cell reduction paralleled transient immunosuppression. Herein we showed that acute oral infection in mice promotes diffuse parasitism in bone marrow cells at 14 and 21 days post-infection (dpi), with perivascular regions, intravascular regions, and regions near the bone being target sites of parasite replication. Phenotypic analysis of hematopoietic differentiation in the bone marrow of infected mice showed that the cell number in the tissue is decreased (lineage-negative and lineage-positive cells). Interestingly, analysis of hematopoietic branching points showed that hematopoietic stem and progenitor cells (HSPCs) were significantly increased at 14 dpi. In addition, the pool of progenitors with stem plasticity (HSC-MPP3), as well as multipotent progenitors (MPPs) such as MPP4, also showed this pattern of increase. In contrast, subsequent progenitors that arise from MPPs, such as common lymphoid progenitors (CLPs), lymphoid-primed MPPs (LMPPs), and myeloid progenitors, were not enhanced; conversely, all presented numeric decline. Annexin V staining revealed that cell death increase in the initial hematopoietic branching point probably is not linked to CLPs and that myeloid progenitors decreased at 14 and 21 dpi. In parallel, our investigation provided clues that myeloid progenitor decrease could be associated with an atypical expression of Sca-1 in this population leading to a remarkable increase on LSK-like cells at 14 dpi within the HSPC compartment. Finally, these results led us to investigate HSPC presence in the spleen as a phenomenon triggered during emergency hematopoiesis due to mobilization or expansion of these cells in extramedullary sites. Splenocyte analysis showed a progressive increase in HSPCs between 14 and 21 dpi. Altogether, our study shows that the bone marrow is a target tissue in T. cruzi orally infected mice, leading to a hematopoietic disturbance with LSK-like cell bias accounting on HSPCs possibly affecting myeloid progenitor numbers. The LMPP and CLP reduction converges with defective thymocyte development. Lastly, it is tempting to speculate that the extramedullary hematopoiesis seen in the spleen is a mechanism involved in the hematological maintenance reported during the acute phase of oral T. cruzi infection. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Complutense University of Madrid. Faculty of Biology. Department of Cell Biology. Madrid, Spain. | pt_BR |
Affilliation | Complutense University of Madrid. Faculty of Biology. Department of Cell Biology. Madrid, Spain. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede de Pesquisa em Neuroimunomodulação do Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede de Pesquisa em Neuroimunomodulação do Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede de Pesquisa em Neuroimunomodulação do Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede de Pesquisa em Neuroimunomodulação do Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Oral infection | pt_BR |
Subject | Bone marrow | pt_BR |
Subject | Thymus | pt_BR |
Subject | Hematopoiesis | pt_BR |
Subject | Hematopoietic stem cells | pt_BR |
Subject | Extramedullary hematopoiesis | pt_BR |
Subject | Multiparametric flow | pt_BR |