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.
Highlights
Trypanosoma brucei is an extracellular protozoan parasite that causes sleeping sickness in humans and nagana in cattle, diseases that still hold a significant socio-economic impact in sub-Saharan Africa[1, 2]
We used a multidisciplinary approach to assess whether an immune response was mounted in adipose tissue (AT) during a T. brucei infection
Given that the signature profile of immune cells is unique and different from all other resident cells of AT[32, 33], we postulated that a transcriptome analysis of infected versus non-infected AT should provide a first glimpse of the type of immune response that is mounted in this tissue
Summary
Trypanosoma brucei is an extracellular protozoan parasite that causes sleeping sickness in humans and nagana in cattle, diseases that still hold a significant socio-economic impact in sub-Saharan Africa[1, 2]. T. brucei transmission to a mammalian host occurs upon the bite of an infected tsetse fly (Glossina spp). Most African trypanosome species are rapidly eliminated by an innate immune trypanosome lytic factor (TLF)[4, 5]. This TLF is delivered by germline-encoded antibodies[6] and promotes complete parasite elimination before the onset of disease. Optimal phagocytosis of T. brucei requires antibody and complement mediated opsonization[7] These antibodies are produced by B cells, plasmocytes (plasmablasts and plasma cells), activated during infection and are directed primarily at the parasite’s variant surface glycoprotein (VSG)[7, 8]. This allows for direct Fc receptor-mediated phagocytosis and for the classical activation of the complement system, followed by phagocytosis
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