P21 activated kinase‐1 (PAK1) in macrophages is required for promotion of Th17 cell response during helminth infection

Abstract

The immune systems, which mainly consist of T cells, B cells and NK cells, are responsible for the maintaining of host homeostasis, adaptive immune responses providing protection against disease and specially infectious disease. 1 In particular, CD4 + T cells different subsets were essential for immune responses during host defence against pathogen infection and inflammatory diseases, 2-7 mainly including Th1, Th2, Th17 and Treg cells. The signals promoting differentiation of naive CD4 + T cells into a particular T helper cell subset are provided by distinct cytokines through activating antigen-presenting cells (APCs). P21-activated kinases 1 (PAK1), which was highly expressed in antigen-presenting cells (APCs), 8,9 contained conserved six serine-threonine kinases and involved in cellular apoptosis, proliferation and migration. 10-12 PAK1 has been reported to play a vital role in variety of disorders such as cancer, Alzheimer's disease, diabetes, and neurofibromatosis. 13 Recent studies have implicated that PAK1 was overexpressed in the inflammation-related disease and promoted cell activation pathways expression involved in

Macrophage regulation & function in helminth infection

“…PAK1 was shown to trigger the activation of inflammatory macrophages, thus inducing IL-6dependent TH17 differentiation and liver pathology in Schistosoma japonicum infection [94].…”

The Developmental Phosphoproteome of Fasciola Gigantica by Shotgun

“…P21-activated protein kinase (PAKs) had long been established to play important roles in vital cellular functions such as proliferation, survival and motility. Emerging evidence showed host PAK1 increased cell survival during the stage of virus infections [39], and recent study found PAK1 enhanced macrophage activation, resulting in promoting of Th17 cell response during Schistosoma japonicum infection [40], both of which guide the future research on the immunomodulation roles of host PAK1 and parasitic PAK1 in Fasciola infection. Camodulins (CaMs) were involved in fundamental processes including the phosphorylation of protein kinases, gene transcription and calcium transport [41].…”

A global phosphoproteomics analysis of adult Fasciola gigantica by LC–MS/MS

“…P21-activated protein kinase (PAKs) had long been established to play important roles in vital cellular functions such as proliferation, survival, and motility (Arias-Romero and Chernoff 2008 ). Emerging evidence showed host PAK1 increased cell survival during the stage of virus infection (Van den Broeke et al 2010 ), and recent study found PAK1 enhanced macrophage activation, resulting in promoting of Th17 cell response during Schistosoma japonicum infection (Chang et al 2020 ), both of which guide the future research on the immunomodulation roles of host PAK1 and parasitic PAK1 in Fasciola infection. To further understand the functions of F. gigantica phosphoproteins annotated in more than 10 KEGG pathways, we took them in comparison with protozoa and helminths to identify possible connections between these phosphoproteins and biological processes of the parasites.…”