Trypanosoma brucei triggers a broad immune response in the adipose tissue

Autor: Sandra Trindade, Filipa Rijo-Ferreira, Tiago Bizarra-Rebelo, Karine Serre, Barbara Rentroia-Pacheco, Luisa M. Figueiredo, Mariana Costa-Sequeira, Henrique Machado, Tânia Carvalho
Přispěvatelé: Repositório da Universidade de Lisboa
Jazyk: angličtina
Rok vydání: 2021
Předmět:
B Cells
Physiology
medicine.medical_treatment
Adipose tissue
ComputingMilieux_LEGALASPECTSOFCOMPUTING
Biochemistry
Parasite load
Mice
White Blood Cells
Medical Conditions
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Biology (General)
Immune Response
Protozoans
0303 health sciences
Immune System Proteins
biology
T Cells
Eukaryota
Acquired immune system
3. Good health
Cytokine
Adipose Tissue
Cellular Types
medicine.symptom
Antibody
Research Article
Trypanosoma
QH301-705.5
Immune Cells
Trypanosoma brucei brucei
Immunology
Inflammation
Trypanosoma brucei
Microbiology
Antibodies
03 medical and health sciences
Immune system
Virology
Parasitic Diseases
Trypanosoma Brucei
Genetics
medicine
Animals
Antibody-Producing Cells
Molecular Biology
030304 developmental biology
Blood Cells
Organisms
Biology and Life Sciences
Proteins
Cell Biology
RC581-607
biology.organism_classification
Parasitic Protozoans
Trypanosomiasis
African
biology.protein
Parasitology
Immunologic diseases. Allergy
Spleen
Trypanosoma Brucei Gambiense
030215 immunology
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
PLoS Pathogens, Vol 17, Iss 9, p e1009933 (2021)
PLoS Pathogens
Popis: Copyright: © 2021 Machado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden.
This work was supported by the European Research Council (FatTryp, ref. 771714) awarded to LMF, by Fundação para a Ciência e Tecnologia (CEECIND/03322/2018) awarded to LMF, (PTDC/MED-IMU/30948/2017 and CEECIND/00697/2018) awarded to KS, (PD/BD/128286/2017) awarded to HM, (SFRH/BPD/89833/2012) awarded to ST, (IMM/BI/83-2017 through PTDC/BIM-MET/4471/2014) awarded to TB-R and by the National Institutes of Health (NIGMS K99GM132557) awarded to FR-F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Databáze: OpenAIRE
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