In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-15), p. e1009933-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009933
DOI:
10.1371/journal.ppat.1009933.g001
DOI:
10.1371/journal.ppat.1009933.g002
DOI:
10.1371/journal.ppat.1009933.g003
DOI:
10.1371/journal.ppat.1009933.g004
DOI:
10.1371/journal.ppat.1009933.g005
DOI:
10.1371/journal.ppat.1009933.g006
DOI:
10.1371/journal.ppat.1009933.s001
DOI:
10.1371/journal.ppat.1009933.s002
DOI:
10.1371/journal.ppat.1009933.s003
DOI:
10.1371/journal.ppat.1009933.s004
DOI:
10.1371/journal.ppat.1009933.s005
DOI:
10.1371/journal.ppat.1009933.s006
DOI:
10.1371/journal.ppat.1009933.s007
DOI:
10.1371/journal.ppat.1009933.s008
DOI:
10.1371/journal.ppat.1009933.s009
DOI:
10.1371/journal.ppat.1009933.s010
DOI:
10.1371/journal.ppat.1009933.s011
DOI:
10.1371/journal.ppat.1009933.s012
DOI:
10.1371/journal.ppat.1009933.s013
DOI:
10.1371/journal.ppat.1009933.r001
DOI:
10.1371/journal.ppat.1009933.r002
DOI:
10.1371/journal.ppat.1009933.r003
DOI:
10.1371/journal.ppat.1009933.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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