title: Third-stage Gnathostoma spinigerum larva excretory secretory antigens modulate function of Fc gamma receptor I-mediated monocytes in peripheral blood mononuclear cell culture.
abstract: BACKGROUND
  Third (infective)-stage Gnathostoma spinigerum larvae (L3) mainly cause human gnathostomiasis. G. spinigerum L3 migrate throughout the subcutaneous tissues, vital organs, and central nervous system and can cause various pathogenesis including sudden death. Interestingly, G. spinigerum L3 can survive and evade host cellular immunity for months or years. The effects of G. spinigerum excretory-secretory (ES) products involved in larval migration and immune-evasive strategies are unknown. Monocytes are innate immune cells that act as phagocytic and antigen-presenting cells and also play roles against helminthic infections via a complex interplay between other immune cells. Fc gamma receptor I (FcγRI) is a high-affinity receptor that is particularly expressed on monocytes, macrophages, and dendritic cells. The cross-linking of FcγRI and antigen-antibody complex initiates signal transduction cascades in phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). This study investigated whether ES antigen (ESA) from G. spinigerum L3 affects monocyte functions.
  
  
  RESULTS
  Cultures of normal peripheral blood mononuclear cells (PBMC) separated from healthy buffy coats were used as a human immune cell model. ESA was prepared from G. spinigerum L3 culture. Using Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the effect of ESA to down-regulate FcγRI mRNA expression in monocytes during 90 min of observation was not well delineated. Flow cytometry analysis revealed a significant phenotypic-decreased FcγRI expression on the monocyte surface at 12 hours (h) of cultivation with the ESA (p = 0.033). Significantly reduced monocyte-mediated phagocytosis capacity was consistently observed after 12 h of ESA pretreatment (p = 0.001).
  
  
  CONCLUSIONS
  Our results suggest that G. spinigerum ESA modulates monocyte function via depletion of FcγRI expression. This study provides preliminary information for future in-depth studies to elucidate mechanisms of the immune-evasive strategy of G. spinigerum larvae.
authors.affiliation: Center of Excellence for Antibody Research, Faculty of Tropical Medicine, Mahidol University, 10400 Bangkok, Thailand.
authors.forename: Surachet
authors.initials: S
authors.lastname: Benjathummarak
authors.affiliation: Pathobiology Unit, Department of Medical Science, Faculty of Science, Rangsit University, Pathumthani, 12000 Thailand.
authors.forename: Ratchanok
authors.initials: R
authors.lastname: Kumsiri
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
authors.forename: Supaporn
authors.initials: S
authors.lastname: Nuamtanong
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
authors.forename: Thareerat
authors.initials: T
authors.lastname: Kalambaheti
authors.affiliation: Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
authors.forename: Jitra
authors.initials: J
authors.lastname: Waikagul
authors.affiliation: Parasitology Unit, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand.
authors.forename: Nareerat
authors.initials: N
authors.lastname: Viseshakul
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
authors.forename: Yaowapa
authors.initials: Y
authors.lastname: Maneerat
keywords: Excretory-secretory; FcγRI; Gnathostoma spinigerum; Monocytes; Phagocytosis