WNT5:FZD7-mediated leishmania damping

Stable Identifier
R-HSA-9673324
Type
Pathway
Species
Homo sapiens
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Wnt-5a (WNT5) is known for being a highly specific regulated gene in response to microbial infection (Blumenthal et al. 2006, Pereira et al. 2008 & Ljungberg et al. 2019) including leishmaniasis (Chakraborty et al. 2017), where it seems to be involve in mechanisms that dampen the parasite load within main host macrophages (Chakraborty et al. 2017). In addition, WNT5 is a highly responsive gene in human macrophages present in chronic diseases such as rheumatoid arthritis (Sen et al. 2000), cancer (Pukrop et al. 2006), atherosclerosis (Christman et al. 2008) and obesity (Ouchi et al. 2010 & Ljungberg et al. 2019).

Frizzled-7 (FZD7) acts as a receptor of WNT5 which, upon binding, is implicated in the initiation of the non-canonical WNT pathway that ends up in the re-accommodation of the cytoskeleton to allow a process called planar cell polarity (PCP) (Ljungberg et al. 2019). The activation of the WNT5:FZD7 non-canonical signalling cascade that drives PCP is being studied for its involvement in inflammatory responses (Shao et al. 2016). Treatment of RAW264.7 macrophages with recombinant Wnt5a induced NADPH oxidase-mediated ROS production, which has been suggested to contribute to the macrophage control of L. donovani. Consequently, detailed understanding of how WNT signaling network defines host responses to infection could be important to identify potential targets (Ljungberg et al. 2019).

Literature References
PubMed ID Title Journal Year
18456733 Wnt5a is expressed in murine and human atherosclerotic lesions

Christman, MA, Goetz, DJ, Dickerson, E, McCall, KD, Lewis, CJ, Benencia, F, Silver, MJ, Kohn, LD, Malgor, R

Am. J. Physiol. Heart Circ. Physiol. 2008
28659356 Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection

Chakraborty, A, Kurati, SP, Mahata, SK, Sundar, S, Roy, S, Sen, M

J. Immunol. 2017
16601243 The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation

Blumenthal, A, Ehlers, S, Lauber, J, Buer, J, Lange, C, Goldmann, T, Heine, H, Brandt, E, Reiling, N

Blood 2006
18174455 Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10

Pereira, C, Schaer, DJ, Bachli, EB, Kurrer, MO, Schoedon, G

Arterioscler. Thromb. Vasc. Biol. 2008
16569699 Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines

Pukrop, T, Klemm, F, Hagemann, T, Gradl, D, Schulz, M, Siemes, S, Trümper, L, Binder, C

Proc. Natl. Acad. Sci. U.S.A. 2006
31781093 Functions of the WNT Signaling Network in Shaping Host Responses to Infection

Ljungberg, JK, Kling, JC, Tran, TT, Blumenthal, A

Front Immunol 2019
20558665 Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity

Ouchi, N, Higuchi, A, Ohashi, K, Oshima, Y, Gokce, N, Shibata, R, Akasaki, Y, Shimono, A, Walsh, K

Science 2010
10688908 Expression and function of wingless and frizzled homologs in rheumatoid arthritis

Sen, M, Lauterbach, K, El-Gabalawy, H, Firestein, GS, Corr, M, Carson, DA

Proc. Natl. Acad. Sci. U.S.A. 2000
Participants
Participates
Disease
Name Identifier Synonyms
cutaneous leishmaniasis DOID:9111 Asian Desert Cutaneous Leishmaniasis, Leproid leishmaniasis, diffuse cutaneous leishmaniasis
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