Wnt signaling contributes to install m2-phenotypic program in t cruzi-infected macrophages

VOLPINI XIMENA; BRUGO, MARÍA BELEN; QUIROZ JUAN NAHUEL; MOTRAN CRISTINA

Virtual

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR .; 2021

Trypanosoma cruzi infection boost a complex immune response inthe host, which involve both innate and adaptative immune cells. Inthis context, macrophages (Mo) represent one of the main targetsfor the parasite. Mo are extremely plastic and respond to environmentalsignals adopting at least two extreme profiles: Classical M1Mo which respond to inflammatory environment increasing CD86 expression,Nitric Oxide (NO) and proinflammatory cytokines production,plays a key role in the control of intracellular parasite growth;whereas Alternative M2 Mo which respond to IL-4 with increasingCD206 and Arg1 expression and anti-inflammatory cytokines release,promotes parasite replication. We have reported that T. cruziinfection induces Wnt signaling activation in Mo, with the inhibitionof Wnt proteins secretion (with IWP-L6) modulating the Mo activationstatus to a more microbicidal phenotype. So, infected Mo thatwere previously treated with IWP-L6, are transcriptionally similar toinfected M1 Mo, although does not fully fit the classical M1 transcriptionalpattern. Here, we aim to evaluate the effect of Wnt signalinginhibition on the phenotype of infected Mo. For that, bone marrowderived Mo were treated with IWP-L6 or Vehicle (V) for 24 h andinfected with T cruzi trypomastigotes (Tps) (Mo:Tps=1:3). Non-infected,LPS+IFN-g- (M1) and IL4-treated (M2) Mo were used ascontrols. Antibody panel for flow cytometry included F4/80, CD11b,CD86, CD206, iNOS and Arg1. We observed that while infection ofMo induces a reduction in the % of CD86+CD206- cells, this effectwas not evident in IWP-L6-treated cultures. In addition, cultures ofinfected IWP-L6-Mo showed lower frequency of total CD206+ cells(p