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Lyz2-specific deletion of IL-4 receptor alpha chain in schistosomiasis does not preclude Ly6Chigh monocytes as the main source of liver macrophages but impairs alternative activation and increase inflammation
Rolot, Marion; Dougall, Annette; Javaux, Justine et al.
2018Molecular and Cellular Biology of Helminth Parasites XII Conference
 

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Abstract :
[en] M(IL-4) accumulate in liver granulomas of Schistosoma mansoni-infected mice from recruited Ly6Chi monocytes and modulate inflammation. Here, we used conditional IL-4 receptor α-chain (IL-4Rα) knockdown Il4ra−/loxlyz2Cre mice to determine whether impairing M(IL-4) modifies the dynamics of Mφ responses in liver granulomas after S. mansoni infection. First, we used reporter RosatdRFP mice crossed with lyz2Cre mice to validate selective Cre-mediated excision in neutrophils and Mφ in naive and S. mansoni infected mice. Next, the liver inflammatory responses were investigated during the first weeks of S. mansoni infection. We observed significantly increased total leukocyte numbers, including monocytes, in the liver by week 8 in Il4ra−/loxlyz2Cre mice while these mice survived the infection similarly to hemizygous Il4ra−/lox mice. When investigating liver monocyte/Mφ responses, we observed that CD11blo resident Küpffer cells (KCs) were severely reducing in term of number over the course of infection and independently of IL-4Rα signalling. While KCs lowered, Ly6Chi monocytes were recruited as soon as week 4 and strongly proliferated by week 8 pi. We further observed that Ly6Chi acquired CD64 expression and converted into Ym1 and Relm-α-expressing CD11bhi Mφ, while these markers were expressed at significantly low levels in Il4ra−/loxlyz2Cre mice. CD11bhi Mφ accumulated at the cost of resident CD11blo KCs, which could suggest that S. mansoni infection causes KC disappearance resulting in recruitment of monocytes to the liver. Indeed, ablation of resident KCs in CD169-DTR mice resulted in the accumulation of a CD11bhi Mφ population similar to the one observed after S. mansoni infection. Thus, our findings indicate that S. mansoni infection is associated with ablation of resident KCs which could in turn result in the accumulation of M(IL-4) in the liver to control granulomatous inflammation.
Disciplines :
Immunology & infectious disease
Author, co-author :
Rolot, Marion
Dougall, Annette
Javaux, Justine
Brombacher, Frank
Dewals, Benjamin G  ;  Université de Liège - ULiège > Immunologie et vaccinologie
Language :
English
Title :
Lyz2-specific deletion of IL-4 receptor alpha chain in schistosomiasis does not preclude Ly6Chigh monocytes as the main source of liver macrophages but impairs alternative activation and increase inflammation
Publication date :
24 September 2018
Event name :
Molecular and Cellular Biology of Helminth Parasites XII Conference
Event place :
Hydra, Greece
Event date :
2-7 September 2018
Audience :
International
Available on ORBi :
since 13 January 2020

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