Pathogens, Vol. 14, Pages 1276: IL-10 Plays a Critical Role in Mitigating Acute Anaemia Development During African Trypanosome Infection

Pathogens doi: 10.3390/pathogens14121276

Authors:
Maida Živalj
Anaïs St. Martin
Patrick De Baetselier
Liudmyla Maksymova
Fara Berghmans
Louis Boon
Jo A. Van Ginderachter
Stefan Magez
Carl De Trez
Benoit Stijlemans

During the first week of T. b. brucei infection, pro-inflammatory IFN-γ production drives acute anaemia by promoting red blood cell clearance by activated macrophages in concert with insufficient bone marrow compensation. The latter is followed by a partial recovery phase, which later progresses to chronic anaemia. To compensate for acute anaemia, stress-induced extramedullary erythropoiesis occurs in the spleen. However, the role of IL-10, a key anti-inflammatory cytokine in regulating stress-induced acute anaemia during African trypanosomosis (AT), remains unclear. Using both genetic and pharmacological approaches, we show that IL-10 is essential to limit acute anaemia by dampening inflammation and promoting splenic erythropoiesis, enabling recovery. More specifically, IL-10 blockade impairs erythropoiesis in both bone marrow and spleen, particularly at early erythroid differentiation stages, and associates with reduced central macrophage (CM) numbers in the bone marrow. In contrast, the co-inhibition of IL-10 and IFN-γ reduces inflammation and partially restores splenic CM numbers and erythropoiesis, highlighting IFN-γ’s suppressive role in erythropoiesis. Overall, these findings underscore IL-10’s key role in regulating stress-induced erythropoiesis during AT by modulating erythroid differentiation and CM abundance, thereby limiting immune-mediated acute anaemia. Consequently, timely adjustment of the IL-10/IFN-γ balance may enhance erythropoiesis and offer a potential therapeutic strategy to mitigate anaemia development.

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Maida Živalj www.mdpi.com