{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:57Z","timestamp":1753891197111,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["22-01026S , 22-14356S , 22-18424M"],"award-info":[{"award-number":["22-01026S , 22-14356S , 22-18424M"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. <jats:italic>Trypanosoma brucei<\/jats:italic> can exploit this by internalising haptoglobin-haemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-\/-) on <jats:italic>T. brucei brucei<\/jats:italic> infection and the parasite\u00b4s capacity to internalise haemoglobin in a Hp-\/- mouse model. The infected Hp-\/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to <jats:italic>T. b. brucei<\/jats:italic>, no differences in the infection response markers of blood plasma between Hp-\/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-\/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-\/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-\/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by <jats:italic>T. b. brucei<\/jats:italic> during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-\/- mice compared to those isolated from Black mice, it suggests that <jats:italic>T. b. brucei<\/jats:italic> employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by <jats:italic>T. b. brucei<\/jats:italic> and offers novel insights into alternative haemoglobin uptake pathways.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1441131","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T07:26:20Z","timestamp":1721287580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Haptoglobin is dispensable for haemoglobin uptake by Trypanosoma 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