@article{fdi:010071385,
  title = {{P}17, an original host defense peptide from ant venom, promotes antifungal activities of macrophages through the induction of {C}-type lectin receptors dependent on {LTB}4-mediated {PPAR} gamma activation},
  author = {{B}enmoussa, {K}. and {A}uthier, {H}. and {P}rat, {M}. and {A}la{E}ddine, {M}. and {L}efevre, {L}. and {R}ahabi, {M}. {C}. and {B}ernad, {J}. and {A}ubouy, {A}gn{\`e}s and {B}onnafe, {E}. and {L}eprince, {J}. and {P}ipy, {B}. and {T}reilhou, {M}. and {C}oste, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{D}espite the growing knowledge with regard to the immunomodulatory properties of host defense peptides, their impact on macrophage differentiation and on its associated microbicidal functions is still poorly understood. {H}ere, we demonstrated that the {P}17, a new cationic antimicrobial peptide from ant venom, induces an alternative phenotype of human monocyte-derived macrophages (h-{MDM}s). {T}his phenotype is characterized by a {C}-type lectin receptors ({CLR}s) signature composed of mannose receptor ({MR}) and {D}ectin-1 expression. {C}oncomitantly, this activation is associated to an inflammatory profile characterized by reactive oxygen species ({ROS}), interleukin ({IL})-1 beta, and {TNF}-alpha release. {P}17-activated h-{MDM}s exhibit an improved capacity to recognize and to engulf {C}andida albicans through the overexpression both of {MR} and {D}ectin-1. {T}his upregulation requires arachidonic acid ({AA}) mobilization and the activation of peroxisome proliferator-activated receptor gamma ({PPAR}.) nuclear receptor through the leukotriene {B}4 ({LTB}4) production. {AA}/{LTB}4/{PPAR} gamma/{D}ectin-1-{MR} signaling pathway is crucial for {P}17-mediated anti-fungal activity of h-{MDM}s, as indicated by the fact that the activation of this axis by {P}17 triggered {ROS} production and inflammasome-dependent {IL}-1 beta release. {M}oreover, we showed that the increased anti-fungal immune response of h-{MDM}s by {P}17 was dependent on intracellular calcium mobilization triggered by the interaction of {P}17 with pertussis toxin-sensitive {G}-protein-coupled receptors on h-{MDM}s. {F}inally, we also demonstrated that {P}17-treated mice infected with {C}. albicans develop less severe gastrointestinal infection related to a higher efficiency of their macrophages to engulf {C}andida, to produce {ROS} and {IL}-1 beta and to kill the yeasts. {A}ltogether, these results identify {P}17 as an original activator of the fungicidal response of macrophages that acts upstream {PPAR} gamma/{CLR}s axis and offer new immunomodulatory therapeutic perspectives in the field of infectious diseases.},
  keywords = {{M}acrophages ; host defense peptide ; antimicrobial peptides ; {C}andida albicans ; {C}-type lectin receptors ; arachidonic acid metabolism ; {PPAR} gamma ; inflammasome},
  booktitle = {},
  journal = {{F}rontiers in {I}mmunology},
  volume = {8},
  numero = {},
  pages = {art. 1650 [15 p.]},
  ISSN = {1664-3224},
  year = {2017},
  DOI = {10.3389/fimmu.2017.01650},
  URL = {https://www.documentation.ird.fr/hor/fdi:010071385},
}