Impact of pulmonary African trypanosomes on the immunology and function of the lung

Dorien Mabille, Laura Dirkx, Sofie Thys, Marjorie Vermeersch, Daniel Montenye, Matthias Govaerts, Sarah Hendrickx, Peter Takac, Johan Van Weyenbergh, Isabel Pintelon, Peter Delputte, Louis Maes, David Pérez-Morga, Jean-Pierre Timmermans and Guy Caljon ()
Additional contact information
Dorien Mabille: University of Antwerp
Laura Dirkx: University of Antwerp
Sofie Thys: University of Antwerp
Marjorie Vermeersch: Université libre de Bruxelles
Daniel Montenye: Université libre de Bruxelles
Matthias Govaerts: University of Antwerp
Sarah Hendrickx: University of Antwerp
Peter Takac: Slovak Academy of Sciences
Johan Van Weyenbergh: Immunology and Transplantation, Rega Institute of Medical Research, KU Leuven
Isabel Pintelon: University of Antwerp
Peter Delputte: University of Antwerp
Louis Maes: University of Antwerp
David Pérez-Morga: Université libre de Bruxelles
Jean-Pierre Timmermans: University of Antwerp
Guy Caljon: University of Antwerp

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role of the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize the lungs and occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. They are present as nests of multiplying parasites exhibiting close interactions with collagen and active secretion of extracellular vesicles. The local immune response shows a substantial increase of monocytes, macrophages, dendritic cells and γδ and activated αβ T cells and a later influx of neutrophils. Interestingly, parasite presence results in a significant reduction of B cells, eosinophils and natural killer cells. T. brucei infected mice show no infection-associated pulmonary dysfunction, mirroring the limited pulmonary clinical complications during sleeping sickness. However, the substantial reduction of the various immune cells may render individuals more susceptible to opportunistic infections, as evident by a co-infection experiment with respiratory syncytial virus. Collectively, these observations provide insights into a largely overlooked target organ, and may trigger new diagnostic and supportive therapeutic approaches for sleeping sickness.

Date: 2022
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DOI: 10.1038/s41467-022-34757-w

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